immunoglobulin genes

Summary

Summary: Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity).

Top Publications

  1. ncbi Production of human antibody repertoires in transgenic mice
    M Bruggemann
    Laboratory of Developmental Immunology and Translocus Therapeutics, Ltd, Babraham Institute, Cambridge, UK
    Curr Opin Biotechnol 8:455-8. 1997
  2. ncbi Predominant autoantibody production by early human B cell precursors
    Hedda Wardemann
    Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA
    Science 301:1374-7. 2003
  3. ncbi A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene
    D Kitamura
    Institute for Genetics, University of Cologne, Germany
    Nature 350:423-6. 1991
  4. pmc High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies
    Hua Xin Liao
    Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, United States
    J Virol Methods 158:171-9. 2009
  5. pmc Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish
    John D Hansen
    Western Fisheries Research Center, Biological Resources Division and Department of Pathobiology, U S Geological Survey and University of Washington, Seattle, WA 98115, USA
    Proc Natl Acad Sci U S A 102:6919-24. 2005
  6. ncbi Positive selection of natural autoreactive B cells
    K Hayakawa
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Science 285:113-6. 1999
  7. ncbi B-1 cells: the lineage question revisited
    L A Herzenberg
    Department of Genetics, Stanford University School of Medicine, CA 94305, USA
    Immunol Rev 175:9-22. 2000
  8. ncbi Molecular mechanisms of antibody somatic hypermutation
    Javier M Di Noia
    Institut de Recherches Cliniques de Montreal, H2W 1R7 Montréal, Quebec, Canada
    Annu Rev Biochem 76:1-22. 2007
  9. ncbi A critical role of lambda 5 protein in B cell development
    D Kitamura
    Institute for Genetics, University of Cologne, Germany
    Cell 69:823-31. 1992
  10. ncbi Editors and editing of anti-DNA receptors
    H Li
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Immunity 15:947-57. 2001

Detail Information

Publications261 found, 100 shown here

  1. ncbi Production of human antibody repertoires in transgenic mice
    M Bruggemann
    Laboratory of Developmental Immunology and Translocus Therapeutics, Ltd, Babraham Institute, Cambridge, UK
    Curr Opin Biotechnol 8:455-8. 1997
    ..Monoclonal antibodies with good affinities for human antigens have been obtained after immunisation. These mice may be a future source of human antibodies for therapy...
  2. ncbi Predominant autoantibody production by early human B cell precursors
    Hedda Wardemann
    Laboratory of Molecular Immunology, Rockefeller University, New York, NY 10021, USA
    Science 301:1374-7. 2003
    ..Most of these autoantibodies were removed from the population at two discrete checkpoints during B cell development. Inefficient checkpoint regulation would lead to substantial increases in circulating autoantibodies...
  3. ncbi A B cell-deficient mouse by targeted disruption of the membrane exon of the immunoglobulin mu chain gene
    D Kitamura
    Institute for Genetics, University of Cologne, Germany
    Nature 350:423-6. 1991
    ..B-cell development in the heterozygous mice seemed to be normal, but in homozygous animals B cells were absent, their development already being arrested at the stage of pre-B-cell maturation...
  4. pmc High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies
    Hua Xin Liao
    Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC, 27710, United States
    J Virol Methods 158:171-9. 2009
    ..These Ig gene expression cassettes constitute a highly efficient strategy for rapid expression of Ig genes for high-throughput screening and analysis without cloning...
  5. pmc Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish
    John D Hansen
    Western Fisheries Research Center, Biological Resources Division and Department of Pathobiology, U S Geological Survey and University of Washington, Seattle, WA 98115, USA
    Proc Natl Acad Sci U S A 102:6919-24. 2005
    ..All three isotypes are primarily expressed in the spleen and pronephros (bone marrow equivalent), and ontogenically, expression of IgT is present 4 d before hatching in developing embryos...
  6. ncbi Positive selection of natural autoreactive B cells
    K Hayakawa
    Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
    Science 285:113-6. 1999
    ..Thus, B cells can be subject to positive selection, generated, and maintained on the basis of their autoreactivity...
  7. ncbi B-1 cells: the lineage question revisited
    L A Herzenberg
    Department of Genetics, Stanford University School of Medicine, CA 94305, USA
    Immunol Rev 175:9-22. 2000
    ....
  8. ncbi Molecular mechanisms of antibody somatic hypermutation
    Javier M Di Noia
    Institut de Recherches Cliniques de Montreal, H2W 1R7 Montréal, Quebec, Canada
    Annu Rev Biochem 76:1-22. 2007
    ..AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors...
  9. ncbi A critical role of lambda 5 protein in B cell development
    D Kitamura
    Institute for Genetics, University of Cologne, Germany
    Cell 69:823-31. 1992
    ..However, the blockade is leaky, allowing B cells to populate the peripheral immune system at a low rate. These cells are allelically excluded and able to respond to antigen...
  10. ncbi Editors and editing of anti-DNA receptors
    H Li
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Immunity 15:947-57. 2001
    ..Among the edited B cells is a subset of multispecific cells that express multiple receptors. One consequence of multispecificity is partial autoreactivity; these multispecific B cells may contribute to autoimmunity...
  11. ncbi The immunoglobulin heavy chain locus of the duck. Genomic organization and expression of D, J, and C region genes
    M L Lundqvist
    Department of Biochemistry and Molecular Biology, Medical University of South Carolina, 173 Ashley Ave, Charleston, SC 29425, USA
    J Biol Chem 276:46729-36. 2001
    ..The duck IgH locus is rich in complex variable number tandem repeats, which occupy approximately 60% of the sequenced region, and occur at a much higher frequency in the IgH locus than in other sequenced regions of the duck genome...
  12. pmc Frequent occurrence of deletions and duplications during somatic hypermutation: implications for oncogene translocations and heavy chain disease
    T Goossens
    Institute for Genetics, University of Cologne, 50931 Cologne, Germany
    Proc Natl Acad Sci U S A 95:2463-8. 1998
    ....
  13. ncbi iHMMune-align: hidden Markov model-based alignment and identification of germline genes in rearranged immunoglobulin gene sequences
    Bruno A Gaëta
    School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia
    Bioinformatics 23:1580-7. 2007
    ..The correct identification of the germline genes that make up a variable VH domain is essential to our understanding of the process of antibody diversity generation as well as to clinical investigations of some leukaemias and lymphomas...
  14. ncbi Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus
    David Jung
    Howard Hughes Medical Institute, Children s Hospital, CBR Institute for Biomedical Research, and Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Immunol 24:541-70. 2006
    ..In this review, we summarize advances that have been made in understanding how V(D)J recombination at the IgH locus is controlled and discuss important areas for future investigation...
  15. ncbi Comparative analyses of immunoglobulin genes: surprises and portents
    Martin F Flajnik
    Department of Microbiology and Immunology, University of Maryland at Baltimore, Baltimore, Maryland 21201, USA
    Nat Rev Immunol 2:688-98. 2002
    The study of immunoglobulin genes in non-mouse and non-human models has shown that different vertebrate groups have evolved distinct methods of generating antibody diversity...
  16. pmc AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations
    Davide F Robbiani
    Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
    Cell 135:1028-38. 2008
    ..Thus, in addition to producing somatic mutations and DNA breaks in antibody genes, AID is also responsible for the DNA lesions in oncogenes that are required for their translocation...
  17. pmc SMUG1 is able to excise uracil from immunoglobulin genes: insight into mutation versus repair
    Javier M Di Noia
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    EMBO J 25:585-95. 2006
    ..The distinction between UNG and overexpressed SMUG1 regarding the balance between antibody diversification and non-mutagenic repair of the U:G lesion could reflect the association of UNG (but not SMUG1) with sites of DNA replication...
  18. ncbi IgH class switching and translocations use a robust non-classical end-joining pathway
    Catherine T Yan
    Howard Hughes Medical Institute, of Genetics, Boston, Massachusetts 02115, USA
    Nature 449:478-82. 2007
    ..In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations...
  19. ncbi Error rate and specificity of human and murine DNA polymerase eta
    T Matsuda
    Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA
    J Mol Biol 312:335-46. 2001
    ..eta), an enzyme that performs translesion DNA synthesis and may participate in somatic hypermutation of immunoglobulin genes. Both mouse and human pol eta lack intrinsic proofreading exonuclease activity and both copy undamaged DNA ..
  20. ncbi Clonal instability of V region hypermutation in the Ramos Burkitt's lymphoma cell line
    W Zhang
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Int Immunol 13:1175-84. 2001
    ..These results suggest that the hypermutation phenotype is inherently unstable in Ramos and that long culture periods favor outgrowth of non-mutating cells that express lower levels of AID...
  21. ncbi SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway
    Sebastian Herzog
    Max Planck Institute for Immunobiology, 79108 Freiburg, Germany
    Nat Immunol 9:623-31. 2008
    ..Together, these data illuminate a molecular function of SLP-65 and identify a key role for Foxo proteins in the regulation of light chain recombination, receptor editing and B cell selection...
  22. ncbi Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire
    Ki Jong Rhee
    Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153, USA
    J Immunol 172:1118-24. 2004
    ..We conclude that specific members of the commensal, intestinal flora drive GALT development through a specific subset of stress responses...
  23. ncbi Cloned transchromosomic calves producing human immunoglobulin
    Yoshimi Kuroiwa
    Pharmaceutical Research Laboratory, Kirin Brewery Co, Ltd, 3 Miyahara cho, Takasaki shi, Gunma 370 1295, Japan
    Nat Biotechnol 20:889-94. 2002
    ..Human immunoglobulin proteins were detected in the blood of newborn calves. The production of Tc calves is an important step in the development of a system for producing therapeutic hPABs...
  24. pmc A large protein containing zinc finger domains binds to related sequence elements in the enhancers of the class I major histocompatibility complex and kappa immunoglobulin genes
    A S Baldwin
    Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139
    Mol Cell Biol 10:1406-14. 1990
    ..Interestingly, expression of MBP-1 mRNA was inducible by mitogen and phorbol ester treatment of Jurkat T cells and by serum treatment of confluent serum-deprived human fibroblasts...
  25. pmc A fetally expressed immunoglobulin VH1 gene belongs to a complex set of alleles
    E H Sasso
    Virginia Mason Research Center, Seattle, Washington 98101
    J Clin Invest 91:2358-67. 1993
    ..We conclude that the 51p1 locus is polymorphic, and that the 51p1 element is the predominant member of a complex set of alleles...
  26. pmc A cis-acting diversification activator both necessary and sufficient for AID-mediated hypermutation
    Artem Blagodatski
    Institute for Molecular Radiobiology, Helmholtz Center Munich, Neuherberg, Germany
    PLoS Genet 5:e1000332. 2009
    ..The results significantly extend previously reported findings on AID-mediated gene diversification. They show by both deletion and insertion analyses that cis-acting sequences predispose neighboring transcription units to hypermutation...
  27. ncbi Subnuclear compartmentalization of immunoglobulin loci during lymphocyte development
    Steven T Kosak
    Department of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, Chicago, IL 60637, USA
    Science 296:158-62. 2002
    ..We suggest that subnuclear positioning represents a novel means of regulating transcription and recombination of IgH and Igkappa loci during lymphocyte development...
  28. pmc Somatic hypermutation introduces insertions and deletions into immunoglobulin V genes
    P C Wilson
    Molecular Immunology Center, Department of Microbiology, University of Texas Southwestern Medical Center at Dallas, Texas 75235 9140, USA
    J Exp Med 187:59-70. 1998
    ....
  29. ncbi AID and mismatch repair in antibody diversification
    Alberto Martin
    Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Chanin 403, Bronx, New York 10461, USA
    Nat Rev Immunol 2:605-14. 2002
  30. pmc Somatic hypermutation and diverse immunoglobulin gene usage in the human antibody response to the capsular polysaccharide of Streptococcus pneumoniae Type 6B
    Jianhui Zhou
    Children s Hospital Oakland Research Institute, Oakland, California 94609, USA
    Infect Immun 72:3505-14. 2004
    ....
  31. ncbi DNA double-strand breaks in immunoglobulin genes undergoing somatic hypermutation
    L Bross
    Basel Institute for Immunology, Grenzacherstrasse 487, CH 4005 Basel, Switzerland
    Immunity 13:589-97. 2000
    ..The introduction of DSBs appears to depend on transcriptional activity. Thus, secondary diversification of rearranged V gene segments relates to an error-prone nonhomologous DSB repair system acting in B cells of the GC...
  32. ncbi Immunoglobulin genes in multiple myeloma: expressed and non-expressed repertoires, heavy and light chain pairings and somatic mutation patterns in a series of 101 cases
    Anastasia Hadzidimitriou
    Hematology Department and Hematopoietic Cell Transplantation Unit, G Papanicolaou Hospital, Thessalonik, Greece
    Haematologica 91:781-7. 2006
    ..We assessed in parallel IGH and IGK/IGL rearrangements in 101 MM patients so as to gain insight into: (i) IG repertoires; (ii) antigen impact; (iii) the role of receptor editing...
  33. pmc Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation
    M Shlomchik
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    J Exp Med 171:265-92. 1990
    ....
  34. ncbi Critical roles of activation-induced cytidine deaminase in the homeostasis of gut flora
    Sidonia Fagarasan
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    Science 298:1424-7. 2002
    ..AID) plays an essential role in class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin genes. We report here that deficiency in AID results in the development of hyperplasia of isolated lymphoid ..
  35. ncbi Oct-2, although not required for early B-cell development, is critical for later B-cell maturation and for postnatal survival
    L M Corcoran
    Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia
    Genes Dev 7:570-82. 1993
    Oct-2, a POU homeo domain transcription factor, is believed to stimulate B-cell-restricted expression of immunoglobulin genes through binding sites in immunoglobulin gene promoters and enhancers...
  36. pmc Allelic exclusion of immunoglobulin genes: models and mechanisms
    Christian Vettermann
    Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA
    Immunol Rev 237:22-42. 2010
    ..We also discuss the physiological consequences of Ig allelic exclusion and speculate on the importance of monospecificity of B cells for immune recognition...
  37. ncbi E2A proteins are required for proper B cell development and initiation of immunoglobulin gene rearrangements
    G Bain
    Department of Biology, University of California, San Diego, La Jolla 92130
    Cell 79:885-92. 1994
    ..In addition, we show that Pax-5 transcripts are significantly reduced in fetal livers of E2A (-/-) mice. These data suggest a crucial role for E2A products as central regulators in early B cell differentiation...
  38. pmc Pax5 induces V-to-DJ rearrangements and locus contraction of the immunoglobulin heavy-chain gene
    Martin Fuxa
    Research Institute of Molecular Pathology, Vienna Biocente, A 1030 Vienna, Austria
    Genes Dev 18:411-22. 2004
    ..Pax5 subsequently activates locus contraction and distal VH-DJH rearrangements in collaboration with an unknown factor that is present in pro-B cells, but absent in thymocytes...
  39. ncbi The Ig(kappa) enhancer influences the ratio of Ig(kappa) versus Ig(lambda) B lymphocytes
    J R Gorman
    Howard Hughes Medical Institute, The Children s Hospital, Boston, Massachusetts 02115, USA
    Immunity 5:241-52. 1996
    ..These studies also imply the existence of additional regulatory elements that have overlapping function with the 3'E(kappa) element...
  40. ncbi The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z
    Nadia Danilova
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, 02139, USA
    Nat Immunol 6:295-302. 2005
    ..This additional class adds complexity to the immunoglobulin repertoire and raises questions concerning the evolution of immunoglobulins and the regulation of the differential expression of ighz and ighm...
  41. pmc IMGT, the international ImMunoGeneTics database
    M P Lefranc
    Laboratoire d Immunogenetique moleculaire, Universite Montpellier II, UPR CNRS 1142 IGH, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Nucleic Acids Res 27:209-12. 1999
    ..IMGT is freely available at http://imgt.cnusc. fr:8104..
  42. ncbi OBF-1, a novel B cell-specific coactivator that stimulates immunoglobulin promoter activity through association with octamer-binding proteins
    M Strubin
    Department of Genetics and Microbiology, University Medical Centre, Geneva, Switzerland
    Cell 80:497-506. 1995
    ..Thus, OBF-1 has all the properties expected for a B cell-specific transcriptional coactivator protein...
  43. ncbi Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region
    C A Reynaud
    Basel Institute for Immunology, Switzerland
    Cell 59:171-83. 1989
    ..Allelic exclusion appears to be performed by restriction of a complete VDJ rearrangement to a single allele...
  44. ncbi Antibodies, immunoglobulin genes and the bursa of Fabricius in chicken B cell development
    Michael J H Ratcliffe
    Department of Immunology, University of Toronto, 1 King s College Circle, Toronto, Ontario, Canada
    Dev Comp Immunol 30:101-18. 2006
    ..This review focuses on the differences between B cell development in the chicken as compared to rodent and primate models...
  45. ncbi Changes in the V(H) gene repertoire of developing precursor B lymphocytes in mouse bone marrow mediated by the pre-B cell receptor
    E ten Boekel
    Basel Institute for Immunology, Switzerland
    Immunity 7:357-68. 1997
    ..These results demonstrate that the pre-B cell receptor in normal mice and the B cell receptor in lambda5-deficient mice mediate a shift in the V(H) repertoire...
  46. pmc The intrinsic hypermutability of antibody heavy and light chain genes decays exponentially
    C Rada
    MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    EMBO J 20:4570-6. 2001
    ..Indeed, quite apart from hot spots, the intrinsic probability of mutation at CDR1 can be almost twice that of CDR3. The analysis has mechanistic implications for current and future models of hypermutation...
  47. ncbi Influence of immunoglobulin heavy- and light-chain expression on B-cell differentiation
    F Young
    Howard Hughes Medical Institute, Children s Hospital, Boston, Massachusetts 02115
    Genes Dev 8:1043-57. 1994
    ....
  48. ncbi A new DNA binding and dimerization motif in immunoglobulin enhancer binding, daughterless, MyoD, and myc proteins
    C Murre
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
    Cell 56:777-83. 1989
    ..Remarkable is the stringent conservation of hydrophobic residues present in both helices. We demonstrate that this new motif plays a crucial role in both dimerization and DNA binding...
  49. pmc Epigenetic and 3-dimensional regulation of V(D)J rearrangement of immunoglobulin genes
    Stephanie C Degner-Leisso
    The Scripps Research Institute, Department of Immunology and Microbial Science, IMM 22, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States
    Semin Immunol 22:346-52. 2010
    ..Taken together, the many epigenetic and 3D layers of control ensure that Ig loci are only rearranged at appropriate stages of B cell development...
  50. ncbi The V(D)J recombination activating gene, RAG-1
    D G Schatz
    Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142
    Cell 59:1035-48. 1989
    ..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself...
  51. ncbi Epstein-Barr virus infection in vitro can rescue germinal center B cells with inactivated immunoglobulin genes
    Sridhar Chaganti
    Cancer Research UK Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham, B15 2TT, United Kingdom
    Blood 106:4249-52. 2005
    ..often arise from atypical post-germinal center B cells, in some cases carrying functionally inactivated immunoglobulin genes. To investigate whether EBV can rescue cells that are failed products of the somatic hypermutation process ..
  52. pmc Variable deletion and duplication at recombination junction ends: implication for staggered double-strand cleavage in class-switch recombination
    X Chen
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku Kyoto 606-8501, Japan
    Proc Natl Acad Sci U S A 98:13860-5. 2001
    ..These findings suggest that single-strand tails of staggered cleavage may be repaired by error-prone DNA synthesis...
  53. ncbi IMGT/JunctionAnalysis: the first tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J JUNCTIONs
    Mehdi Yousfi Monod
    Laboratoire d ImmunoGenetique Moleculaire LIGM, Universite Montpellier II, UPR CNRS 1142, Institut de Genetique Humaine IGH, Montpellier Cedex 5, France
    Bioinformatics 20:i379-85. 2004
    ..We developed IMGT/JunctionAnalysis to analyse automatically in detail the IG and TR junctions, according to the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts...
  54. ncbi Altering the pathway of immunoglobulin hypermutation by inhibiting uracil-DNA glycosylase
    Javier Di Noia
    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, UK
    Nature 419:43-8. 2002
    ..This is good evidence that antibody diversification involves dC --> dU deamination within the immunoglobulin locus itself...
  55. ncbi Hypermutation in shark immunoglobulin light chain genes results in contiguous substitutions
    Susan S Lee
    Department of Physiology and Pharmacology, The State University of New York Health Science Center at Brooklyn, Brooklyn, NY 11203, USA
    Immunity 16:571-82. 2002
    ..We suggest this is one of several pathways of hypermutation diversifying shark antigen-receptor genes--point mutations, tandem mutations, and mutations with a G-C preference--that coevolved with or preceded gene rearrangement...
  56. ncbi Evolution of antigen binding receptors
    G W Litman
    Department of Pediatrics, University of South Florida College of Medicine, All Children s Hospital, St Petersburg 33701, USA
    Annu Rev Immunol 17:109-47. 1999
    ....
  57. pmc Induction of Ig light chain gene rearrangement in heavy chain-deficient B cells by activated Ras
    A C Shaw
    Howard Hughes Medical Institute, Boston, MA 02115, USA
    Proc Natl Acad Sci U S A 96:2239-43. 1999
    ..We discuss these findings in the context of potential mechanisms that may regulate Ig LC gene rearrangement...
  58. ncbi Organization and expression of the lambda-like genes that contribute to the mu-psi light chain complex in human pre-B cells
    D Bossy
    Centre d Immunologie INSERM CNRS de Marseille Luminy, France
    Int Immunol 3:1081-90. 1991
    ..Only the full-length transcript could encode a functional polypeptide chain corresponding to the 22 kDa light chain surrogate...
  59. ncbi Involvement of DNase gamma in the resected double-strand DNA breaks in immunoglobulin genes
    Mariko Okamoto
    Division of Molecular Biology, Research Institute for Biological Sciences, Tokyo University of Science, 2669 Yamazaki, Noda, Chiba 278 0022, Japan
    Biochem Biophys Res Commun 327:76-83. 2005
    ..Conversely, a selective DNase gamma inhibitor, DR396, suppressed the generation of the resected DSBs. These results suggest that DNase gamma is involved in the generation of resected DSBs associated with SHM...
  60. ncbi Functional homology between N-myc and c-myc in murine plasmacytomagenesis: plasmacytoma development in N-myc transgenic mice
    Y Wang
    Department of Tumor Biology, Karolinska Institute, Stockholm, Sweden
    Oncogene 7:1241-7. 1992
    ..All plasmacytomas expressed the N-myc transgene, while none of them expressed either c-myc or endogenous N-myc. None of the tumors carried the usual plasmacytoma-associated translocations...
  61. ncbi The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias
    Annick Lim
    Unité de Recherche et d Expertise Immunité anti virale, Biothérapie et Vaccins, Paris, France Inserm U668, Institut Pasteur, Paris, France
    J Allergy Clin Immunol 120:696-706. 2007
    ..Patients with atopic diseases are characterized by high levels of specific IgE production. However, little is known about the composition of their B-cell repertoires...
  62. ncbi Regulation of an early developmental checkpoint in the B cell pathway by Ig beta
    S Gong
    Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    Science 272:411-4. 1996
    ..These experiments define an unexpected, early requirement for Ig(beta) to produce B cells that can complete VDJH recombination...
  63. ncbi Physical location of the human immunoglobulin lambda-like genes, 14.1, 16.1, and 16.2
    T R Bauer
    University of Miami School of Medicine, Department of Microbiology and Immunology, FL 33101
    Immunogenetics 38:387-99. 1993
    ..Consistent with the GenBank nomenclature, these human IGLL genes will be referred to as IGLL1 (14.1), IGLL2 (16.2), and IGLL3 (16.1), reflecting their position on chromosome 22, as established by this report...
  64. ncbi VH gene usage in immunoglobulin E responses of seasonal rhinitis patients allergic to grass pollen is oligoclonal and antigen driven
    J M Davies
    Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Commercial Road, Melbourne, VIC 3004, Australia
    Clin Exp Allergy 34:429-36. 2004
    ....
  65. ncbi Independent control of immunoglobulin switch recombination at individual switch regions evidenced through Cre-loxP-mediated gene targeting
    H Gu
    Institute for Genetics, University of Cologne, Federal Republic of Germany
    Cell 73:1155-64. 1993
    ....
  66. ncbi V lambda-J lambda rearrangements are restricted within a V-J-C recombination unit in the mouse
    P Sanchez
    Unite d Immunochimie Analytique, Departement d Immunologie, Institut Pasteur, Paris, France
    Eur J Immunol 21:907-11. 1991
    ..Our results also provide no evidence for the use of undescribed segments as has been recently suggested by the finding of the V lambda x segment...
  67. ncbi On the molecular mechanism of somatic hypermutation of rearranged immunoglobulin genes
    Andrew Franklin
    Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia
    Immunol Cell Biol 82:557-67. 2004
    ..Quantitative analysis, in the context of extant data that define the features of SHM, favours the RNA-dependent mechanism...
  68. pmc Expression of error-prone polymerases in BL2 cells activated for Ig somatic hypermutation
    V Poltoratsky
    Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 98:7976-81. 2001
    ..However, pols iota, eta, and zeta are present under all conditions, suggesting that their presence is not sufficient to generate mutations because both T cell and IgM stimuli are required for SHM induction...
  69. ncbi Expression of individual immunoglobulin genes occurs in an unusual system consisting of multiple independent loci
    Donna D Eason
    Department of Molecular Genetics, All Children s Hospital, St Petersburg, FL, USA
    Eur J Immunol 34:2551-8. 2004
    ..Taken together, these findings suggest that a mechanism for haplotype exclusion arose early in the evolution of antibody diversity and is independent of a single genetic locus...
  70. ncbi Targeting of AID to immunoglobulin genes
    Ursula Storb
    Department of Molecular Genetics and Cell Biology, University of Chicago, USA
    Adv Exp Med Biol 596:83-91. 2007
  71. pmc Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells
    Camil E Sayegh
    Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093, USA
    Genes Dev 19:322-7. 2005
    ..Based on these observations, we propose that Ig loci are repositioned by a looping mechanism prior to IgH V(D)J rearrangement to facilitate the joining of Ig variable, diversity, and joining segments...
  72. ncbi Characteristics of immunoglobulin gene usage of the xenoantibody binding to gal-alpha(1,3)gal target antigens in the gal knockout mouse
    S Nozawa
    Transplantation Biology Research Laboratory, Division of Cardiothoracic Surgery, The Keck School of Medicine, University of Southern California, Los Angeles 90027, USA
    Transplantation 72:147-55. 2001
    ..Gal o/o mouse can serve as a useful model for examining the genetic control of antibody/antigen interactions associated with the humoral response to pig xenografts in humans...
  73. ncbi Mechanisms of B-cell lymphoma pathogenesis
    Ralf Kuppers
    Institute for Cell Biology Tumor Research, University of Duisburg Essen, Medical School, Germany
    Nat Rev Cancer 5:251-62. 2005
    ..Recent insights into the lymphomagenic role of factors supplied by the microenvironment also offer new therapeutic strategies...
  74. pmc IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences
    Veronique Giudicelli
    IMGT, the international ImMunoGeneTics information system, Laboratoire d Immunogenetique moleculaire, LIGM, Universite Montpellier II, Institut de Genetique Humaine IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Nucleic Acids Res 34:D781-4. 2006
    ..They represent the main source of IG and TR gene and allele knowledge stored in IMGT/GENE-DB and in the IMGT reference directory. IMGT/LIGM-DB is freely available at http://imgt.cines.fr...
  75. ncbi Contribution of receptor editing to the antibody repertoire
    R Casellas
    Laboratory of Molecular Immunology, Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021, USA
    Science 291:1541-4. 2001
    ..These results suggest that receptor editing represents a major force in shaping the antibody repertoire...
  76. pmc Immunoglobulin kappa light chain variable region gene complex organization and immunoglobulin genes encoding anti-DNA autoantibodies in lupus mice
    R Kofler
    Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037
    J Clin Invest 82:852-60. 1988
    ..These data argue against abnormalities in the genes and mechanisms generating antibody diversity in lupus mice and suggest a remarkable genetic and structural diversity in the generation of anti-DNA binding sites...
  77. ncbi AID mutates a non-immunoglobulin transgene independent of chromosomal position
    Jahan Yar Parsa
    Department of Immunology, University of Toronto, Medical Sciences Bldg, Toronto, Canada M5S 1A8
    Mol Immunol 44:567-75. 2007
    ....
  78. ncbi Stat5 mediates the IL-7-induced accessibility of a representative D-Distal VH gene
    Michelle L Stanton
    Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA 02111, USA
    J Immunol 174:3164-8. 2005
    ..Lastly, as with all known Stat5 target genes, A1 germline transcription requires a deacetylase activity. These results demonstrate that in response to IL-7 signaling, Stat5 is recruited to the D-distal A1 gene and induces accessibility...
  79. ncbi Ig heavy chain protein controls B cell development by regulating germ-line transcription and retargeting V(D)J recombination
    M S Schlissel
    Department of Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205
    J Immunol 153:1645-57. 1994
    ..We propose that membrane-associated mu protein regulates B cell development by signaling a change in the pattern of unrearranged Ig gene transcriptional activity, thereby retargeting the V(D)J recombinase...
  80. ncbi Gene conversion in human rearranged immunoglobulin genes
    John M Darlow
    Department of Immunology, Level 4, Glasgow Biomedical Research Centre, 120 University Place, Glasgow, G12 8TA, UK
    Immunogenetics 58:511-22. 2006
    ..show replacement of central sections by a sequence from another gene, similar to gene conversion in the immunoglobulin genes of other species...
  81. pmc Pax5 is required for recombination of transcribed, acetylated, 5' IgH V gene segments
    David G T Hesslein
    Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520 8011, USA
    Genes Dev 17:37-42. 2003
    ..The finding of transcribed, histone acetylated gene segments that fail to recombine suggests that a Pax5-dependent regulatory mechanism is required in addition to standard constraints of accessibility to control V(H) gene recombination...
  82. ncbi PU.1 as a chromatin accessibility factor for immunoglobulin genes
    Sylvia Marecki
    Department of Medicine, Boston University School of Medicine, 650 Albany Street X 438, Boston, MA 02118, USA
    Mol Immunol 40:723-31. 2004
    ..We conclude that PU.1 is a context-dependent chromatin accessibility factor that, alone, cannot establish widespread accessibility required for critical developmental processes such as antigen receptor recombination...
  83. ncbi Antigen-specific human monoclonal antibodies from mice engineered with human Ig heavy and light chain YACs
    L L Green
    Cell Genesys, Inc, Foster City, California 94404
    Nat Genet 7:13-21. 1994
    ..These strains should provide insight into the adoptive human antibody response and permit the development of fully human monoclonal antibodies with therapeutic potential...
  84. pmc Insertion of phosphoglycerine kinase (PGK)-neo 5' of Jlambda1 dramatically enhances VJlambda1 rearrangement
    T Sun
    Department of Molecular Genetics and Cell Biology, University of Chicago, 920 E 58th St, Chicago, IL 60637, USA
    J Exp Med 193:699-712. 2001
    ....
  85. pmc Malleable immunoglobulin genes and hematopathology - the good, the bad, and the ugly: a paper from the 2007 William Beaumont hospital symposium on molecular pathology
    Adam Bagg
    Hematology, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 7 103 Founders Pavilion, 3400 Spruce St, Philadelphia, PA 19104 4283, USA
    J Mol Diagn 10:396-410. 2008
    ..An appreciation of the various mechanisms involved in the numerous physiological pathways affecting the immunoglobulin genes, and hence antibody molecules, is central to an understanding of B-cell development vis-à-vis the ..
  86. ncbi Molecular analysis of immunoglobulin genes in primary intraocular lymphoma
    Sarah E Coupland
    Department of Pathology, Charite University Hospital Berlin, Campus Benjamin Franklin, Germany
    Invest Ophthalmol Vis Sci 46:3507-14. 2005
    ..To analyze somatic hypermutations in clonally rearranged IgH chain variable (V) genes of primary intraocular lymphoma (PIOL), to identify the differentiation stage of B-PIOL cells...
  87. ncbi PCR cloning of human immunoglobulin genes
    James D Marks
    Department of Anesthesia, University of California, San Francisco, San Francisco General Hospital, USA
    Methods Mol Biol 248:117-34. 2004
  88. pmc The coupling between enhancer activity and hypomethylation of kappa immunoglobulin genes is developmentally regulated
    D E Kelley
    Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111
    Mol Cell Biol 8:930-7. 1988
    ..The change in methylation status, together with associated changes in chromatin structure, may suffice to eliminate or lessen the importance of the enhancer for the maintenance of the transcriptionally active state...
  89. ncbi Repertoire selection by pre-B-cell receptors and B-cell receptors, and genetic control of B-cell development from immature to mature B cells
    F Melchers
    The Basel Institute for Immunology, Switzerland
    Immunol Rev 175:33-46. 2000
    ..Furthermore, the transition of immature B cells from the bone marrow to spleen and their development to mature cells appear as two separate steps controlled by different genes...
  90. ncbi Oligodendrocyte-reactive O1, O4, and HNK-1 monoclonal antibodies are encoded by germline immunoglobulin genes
    K Asakura
    Department of Neurology, Mayo Clinic and Foundation, Rochester, MN 55905, USA
    Brain Res Mol Brain Res 34:283-93. 1995
    ..O1 and O4, but not A2B5 were polyreactive against multiple antigens by direct ELISA. Therefore, O1, O4 and HNK-1 Igs are encoded by germline genes, and have the genotype and phenotype of natural autoantibodies...
  91. pmc Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes
    Vladimir I Mayorov
    Mercer University School of Medicine, Macon, GA 31207, USA
    BMC Immunol 6:10. 2005
    ..The DNA sequence context of mutation hotspots at G-C pairs during SHM is DGYW/WRCH (G-C is a hotspot position, R = A/G, Y = T/C, W = A/T, D = A/G/T)...
  92. ncbi A second B cell-specific enhancer 3' of the immunoglobulin heavy-chain locus
    S Pettersson
    Medical Research Council Laboratory of Molecular Biology, Cambridge, UK
    Nature 344:165-8. 1990
    ..The IgH 3' enhancer could therefore play a part in the activation of the translocated c-myc genes in rat immunocytomas, mouse plasmacytomas and Burkitt lymphomas...
  93. ncbi The human antibody repertoire to infectious agents: implications for disease pathogenesis
    Mats Ohlin
    Wallenberg Laboratory, Department of Immunotechnology, Lund University, P O Box 7031, S 22007 Lund, Sweden
    Mol Immunol 40:1-11. 2003
    ....
  94. pmc Recurrent variable region gene usage and somatic mutation in the human antibody response to the capsular polysaccharide of Streptococcus pneumoniae type 23F
    Jianhui Zhou
    Children s Hospital Oakland Research Institute, Oakland, California 94609, USA
    Infect Immun 70:4083-91. 2002
    ..Lastly, analysis of the isolated Fabs indicate all have undergone extensive somatic mutation, as well as class switch, maturational events that presumably require the participation of T cells...
  95. ncbi The immunoglobulin IGHD gene locus in C57BL/6 mice
    Jian Ye
    National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bldg 38A, Room 1003K, Bethesda, MD 20894, USA
    Immunogenetics 56:399-404. 2004
    ..There are also differences in the coding regions of the DST4 and DQ52 genes between the two mouse strains...
  96. ncbi Fas is required for clonal selection in germinal centers and the subsequent establishment of the memory B cell repertoire
    Y Takahashi
    Department of Immunology, National Institute of Infectious Diseases, 1 23 1 Toyama, Shinjuku ku, 162 8640, Tokyo, Japan
    Immunity 14:181-92. 2001
    ..These results suggest that Fas is required for clonal selection within GCs and the establishment of the memory B cell repertoire...
  97. ncbi Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes
    H M Shen
    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60617, USA
    Science 280:1750-2. 1998
    ..Significant mutations were not observed in c-MYC, S14, or alpha-fetoprotein (AFP) genes, but BCL-6 was highly mutated in a large proportion of memory B cells of normal individuals. The mutation pattern was similar to that of Ig genes...
  98. pmc IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes
    Veronique Giudicelli
    IMGT, the international ImMunoGeneTics information system, Laboratoire d Immunogenetique moleculaire, LIGM, Universite Montpellier II, Institut de Genetique Humaine, IGH, UPR CNRS 1142, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France
    Nucleic Acids Res 33:D256-61. 2005
    ..IMGT/GENE-DB is freely available at http://imgt.cines.fr...
  99. ncbi Requirement of the activation-induced deaminase (AID) gene for immunoglobulin gene conversion
    Hiroshi Arakawa
    Department of Cellular Immunology, Heinrich Pette Institute, Martinistrasse 52, 20251 Hamburg, Germany
    Science 295:1301-6. 2002
    ..This demonstrates that the AID master gene controls all B cell-specific modifications of vertebrate Ig genes...
  100. ncbi Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice
    E Spanopoulou
    Rockefeller University, New York, New York
    Genes Dev 8:1030-42. 1994
    ..These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process...
  101. ncbi Class-switch recombination: interplay of transcription, DNA deamination and DNA repair
    Jayanta Chaudhuri
    Howard Hughes Medical Institute, Center for Blood Research and Department of Genetics, Harvard University Medical School, Boston, Massachusetts 02115, USA
    Nat Rev Immunol 4:541-52. 2004

Research Grants63

  1. Regulation and Dysregulation of Antibody Diversification
    MATTHEW STROUT; Fiscal Year: 2013
    ..center B cells and is required for somatic hypermutation (SHM) and class switch recombination (CSR) of immunoglobulin genes. Aberrant targeting of AID to proto-oncogenes has also been implicated in the pathogenesis of B cell ..
  2. Biochemical Basis of Somatic Hypermutation
    MYRON GOODMAN; Fiscal Year: 2013
    ..a member of the APOBEC family of nucleic acid cytidine deaminases, converts C?U during transcription of immunoglobulin genes to initiate SHM and CSR...
  3. Mucosal Immune Ontogeny and Intestinal Microbiota in Infants
    Edward N Janoff; Fiscal Year: 2010
    ..g., Bacteroides and Clostridium species) are implicated in driving the development and diversity of the immunoglobulin genes that determine the diversity of the humoral immune repertoire...
  4. Immunoglobulin Constant Region Switch and Hypermutation in the Nurse Shark
    Ellen Hsu; Fiscal Year: 2012
    ..PUBLIC HEALTH RELEVANCE: Our shark model system carries about 85 immunoglobulin genes that are targeted by enzymes introducing nicks or lesions in the course of generating antibody diversity...
  5. Immune complexes: origins and effects in HCV infection
    Lynn B Dustin; Fiscal Year: 2013
    ..or HCV-neutralizing antibody will be characterized by cloning and sequencing of the rearranged expressed immunoglobulin genes. This will permit us to define the immunoglobulin repertoire associated with reactivity to HCV...
  6. Error Correction in DNA Synthesis: A Biochemical Study
    MYRON GOODMAN; Fiscal Year: 2013
    ..the properties of DNA-dependent cytidine deaminases involved in the initiation of somatic hypermutation in immunoglobulin genes and inactivation of HIV-1...
  7. HPV CAPSID ANTIBODIES
    Denise A Galloway; Fiscal Year: 2013
    ..that can be identified using Solexa sequencing technology to sequence segments of the rearranged V(D)J immunoglobulin genes, coupled with computational analyses...
  8. Somatic Diversification of Immunoglobulin Genes in GALT
    Katherine L Knight; Fiscal Year: 2013
    ....
  9. Mismatch repair in V region mutation and isotype switching
    Matthew D Scharff; Fiscal Year: 2013
    ..by applicant): Germinal center B cells undergo a high rate of somatic mutation and recombination of their immunoglobulin genes that is responsible for the affinity maturation and isotype switching that generates protective antibodies...
  10. Germline-Specific Immunogens for the Induction of Neutralizing Antibodies to HIV-
    ROBERT GERALD WHALEN; Fiscal Year: 2013
    ..Because any individual germline sequence represents only a few percent of all rearranged immunoglobulin genes, activating specific B cells with germline-specific immunogens could increase the likelihood of inducing an ..
  11. Phase I, Open-Label Dose-Escalation
    Januario E Castro; Fiscal Year: 2010
    ..Such alterations, along with the clonal expression of somatically generated immunoglobulin genes, may direct expression of "altered-self" proteins that could be targeted by the patient's immune ..
  12. Large-Scale Characterization of Autoantibody Responses in Rheumatoid Arthritis
    William H Robinson; Fiscal Year: 2013
    ..antibody-expressing cells, thereby enabling high-throughput analysis of the paired heavy- and light-chain immunoglobulin genes expressed by single B cells, plasmablasts, or plasma cells...
  13. The Immunoglobulin Gene Usage for Anti-V3 Monoclonal Antibodies
    Miroslaw K Gorny; Fiscal Year: 2010
    ..Identifying the immunoglobulin genes that encode the most potent neutralizing antibodies will be essential when designing an effective HIV ..
  14. Non-Human primate models for human xenotransplantation
    Mary K Kearns Jonker; Fiscal Year: 2010
    ..This grant proposal will extend our work in the previous grant period in which we defined the structure of immunoglobulin genes encoding xenoantibodies to wild type pig organs in non-human primates and have identified an anti-idiotypic ..
  15. Anti-Idiotype Therapy of Human B Cell Malignancy
    Ronald Levy; Fiscal Year: 2007
    ..Viral vectors will be developed for the introduction of immunoglobulin genes into dendritic cells, which in turn will be tested for vaccine potency...
  16. AID in somatic mutation of immunoglobulin genes
    URSULA B STORB; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The process of somatic hypermutation (SHM) of immunoglobulin genes is initiated by the cytidine deaminase AID creating cytidine (C) to uridine (U) transition mutations...
  17. GENE CONVERSION IN MYC INDUCED BURSAL LYMPHOMAS
    Craig Thompson; Fiscal Year: 2001
    ..gene conversion is a normal developmental process that is used to generate diversity within the rearranged immunoglobulin genes of avian species...
  18. TISSUE SPECIFIC GENE EXPRESSION
    Huntington Potter; Fiscal Year: 1990
    Transcription from Recombinationally Activated Immunoglobulin Genes. Specialized nucleic acid elements are involved in the expression of immunoglobulin genes. These elements are 'enhancers' which act positively to promote transcription...
  19. EXPRESSION OF IMMUNOGLOBULIN GENES IN TRANSGENIC MICE
    Ursula Storb; Fiscal Year: 2000
    ..It is expected that these experiments will contribute to the understanding of the control of B cell development and Ig gene expression, and will provide new insights into immunological disorders with a B cell component. ..
  20. OPHTHALMOPATHY OF GRAVES DISEASE
    Juan Jaume; Fiscal Year: 2001
    ..3)Molecular Cloning and expression of immunoglobulin genes from orbital plasma cells in Graves' ophthalmopathy:- (i) Construction of combinatorial IgG heavy (H) and ..
  21. IMMUNOGLOBULIN GENE TARGETING INTO THE MOUSE GERM LINE
    Matthias Wabl; Fiscal Year: 1992
    ..longstanding problems in B lymphocyte differentiation is attempted: the mechanism of allelic exclusion of immunoglobulin genes, the generation of the antibody repertoire, and the function on immunoglobulin D (IgD)...
  22. POLYADENYLATION OF MESSENGER RNA PRECURSORS REGULATION
    PHILLIP SHARP; Fiscal Year: 1990
    ..definitely proven it is likely that the regulated synthesis of the two forms of mRNAs for the heavy chain immunoglobulin genes is due to regulation of the efficiency of polyadenylation at the two sites...
  23. CHARACTERIZATION OF AUTOANTIBODIES IN IMMUNE CYTOPENIAS
    Denise Shaw; Fiscal Year: 1992
    ..autoreactive B cell lines generated by the proposed activities will be tools for characterizing specific immunoglobulin genes that encode autoantibodies in AITP and AIHA...
  24. GENETIC ANALYSIS OF HUMAN LYMPHOID NEOPLASIA
    Jeffrey Sklar; Fiscal Year: 1991
    ..A last set of studies concerns somatic mutation in immunoglobulin genes of lymphoid neoplasms...
  25. GENETICS OF INHIBITOR FORMATION IN HEMOPHILIA
    Joan Gill; Fiscal Year: 2001
    ..then be examined through fine mapping of polymorphic markers in the regions of interest, including the MHC, immunoglobulin genes, the T-cell receptor genes, and selected cytokine and cytokine receptor genes...
  26. MOLECULAR PATHOLOGY OF LEUKEMIA/LYMPHOID MARKER
    KAREN CHANCELLOR; Fiscal Year: 1993
    ..Integration of these data will yield a comprehensive picture of structure/ function correlates of this gene in normal and leukemic cells...
  27. STRUCTURE AND DIVERSITY IN THE IMMUNE SYSTEM
    Lisa Steiner; Fiscal Year: 1992
    ..increase our understanding of the range of diversity in the immune system by examining immunoglobulins and immunoglobulin genes in the developing amphibian, Xenopus laevis...
  28. EARLY EVOLUTIONARY ORIGINS OF IMMUNOGLOBULIN GENES
    GARY LITMAN; Fiscal Year: 2003
    ..Such studies are of profound significance in terms of our understanding the basis for immunological recognition and diseases of the immune system, including malignancy. ..
  29. TUMOR CELL KILLING BY EXPRESSION OF A TOXIN GENE
    IAN MAXWELL; Fiscal Year: 1992
    ..in DT- A expression constructs with specificity for B-lymphoid cells using regulatory elements from immunoglobulin genes, 2) To target DT-A expression to subsets of B-lymphoid cells using lg light chain or MHC class II gene ..
  30. SELF-TOLERANCE DEFECTS IN DRUG-INDUCED AUTOIMMUNITY
    Robert Rubin; Fiscal Year: 1999
    ..specificity driven by chromatin-reactive T cells and endogenous chromatin will be traced by sequencing the immunoglobulin genes of the expressed autoantibody repertoire immortalized in B cell hybridomas...
  31. Dissecting the protective and pathogenic functions of TNF alpha in SLE
    Weiqing Huang; Fiscal Year: 2009
    ..mechanism of induction of anti-DNA antibodies and disease in SLE prone mice bearing knock-in autoreactive immunoglobulin genes. To understand how TNFa is pathogenic in the setting of nephritis we will use therapeutic TNFa or TNFR ..
  32. IMMUNOGLOBULIN GENES AS MARKERS FOR RESIDUAL ALL
    Richard Smith; Fiscal Year: 1991
    ..A trial will be initiated to test the power of this assay to predict hematologic relapse...
  33. MUCOSAL DEFENSE BY IGA AGAINST S PNEUMONIAE
    Edward Janoff; Fiscal Year: 2005
    ..g., mutation rates of immunoglobulin genes (VH), momeric, polymeric, and secretory structure of IgA, avidity, and pattern of IgA glycosylation) ..
  34. GENOMIC DOMAINS AND TOPOISOMERASES IN GENE REGULATION
    HAROLD MARTINSON; Fiscal Year: 1990
    ..We will then examine the association of topoisomerase II with known enhancers in the immunoglobulin genes to determine if this association is tissue specific...
  35. GENETIC STUDIES OF HUMAN B CELL CANCER
    Jeffrey Sklar; Fiscal Year: 1992
    ..4) Investigation of somatic hypermutation in rearranged immunoglobulin genes of B cell lymphomas and cell lines...
  36. Duck Antibody Genes: Unusual Organization and Expression
    Gregory Warr; Fiscal Year: 2007
    ..goal of the proposed studies is to understand the genetic mechanisms controlling the expression of duck immunoglobulin genes. The duck has an immune response that can be characterized as ineffectual, which has significance for human ..
  37. TUMOR SUPPRESSIVE T CELLS WITH FCR IN MYELOMA
    RICHARD HOOVER; Fiscal Year: 1993
    ..In addition, IBF can also suppress the transcription of immunoglobulin genes by suppressing the function of immunoglobulin enhancers...
  38. MOLECULAR GENETICS OF HUMAN MULTIPLE MYELOMA
    MICHAEL WIILLIAMS; Fiscal Year: 1992
    ..and characterization of the EBX heavy chain insertion, to develop restriction maps of other aberrant MM immunoglobulin genes, and to clone and characterize by hybridization and DNA sequencing analysis certain flanking sequences from ..
  39. EXPRESSION OF IMMUNOGLOBULIN GENES
    Ursula Storb; Fiscal Year: 2005
    ..Unraveling B cell development should help in understanding the basis of these diseases. ..
  40. Large Scale Images of Gene Transcription in MS and EAE
    Lawrence Steinman; Fiscal Year: 2004
    ..of active and chronic lesions, where we have already identified key differences in transcription of immunoglobulin genes p38kinase and alpha-1-antichymotrypsin...
  41. STRUCTURE AND DIFFERENTIATION OF IMMUNOGLOBULIN GENES
    Janet Stavnezer; Fiscal Year: 1980
    The Structure and Differentiation of Immunoglobulin Genes: I propose to determine the number, and study the structure and differentiation of immunoglobulin genes by molecular hybridization and cloning procedures...
  42. MOLECULAR CLONING AND EXPRESSION OF HUMAN ANTI-GP120
    Roland Newman; Fiscal Year: 1991
    ..The intent here is to clone immunoglobulin genes from single B cells which express the latter type of antibody, after they have been expanded in vitro...
  43. ASSEMBLY AND EXPRESSION OF IG VARIABLE REGION GENES
    Frederick Alt; Fiscal Year: 2000
    ....
  44. TRANSGENIC ANIMAL MODELS USING YACS
    THEODORE CHOI; Fiscal Year: 1992
    ..Finally, these mice will be bred with mice lacking functional endogenous immunoglobulin genes. Hybridomas will be generated at various stages of the project from their offspring to determine if somatic ..
  45. IDIOTYPES OF RHEUMATOID FACTORS
    George Moxley; Fiscal Year: 1990
    ..The proposed research will compare immunoglobulin genes among rheumatoid synovium and cells of RF-positive individuals with diseases other than RA by means of ..
  46. GENETIC VARIATION IN B LYMPHOCYTE ONTOGENY
    Matthias Wabl; Fiscal Year: 2000
    ..Thus, in the segments of immunoglobulin genes that encode the variable (V) regions of antibodies, mutations are beneficial...
  47. Human Polyclonal Antibody Production in Chickens
    Philip Leighton; Fiscal Year: 2002
    ..The proposed research in Phase I will test whether human immunoglobulin genes can be properly processed and expressed in the context of the chicken immune system...
  48. DEVELOP MENTAL CONTROL OF XENOPUS IMMUNOGLOBULIN GENES
    GARY LITMAN; Fiscal Year: 1991
    ..Such findings have far reaching significance in terms of our understanding the developmental regulation of eukaryotic gene expression and the ontogenesis of adaptive immunity...
  49. ATTACHMENT SITE RECOGNITION IN PHAGE LAMBDA INTEGRATION
    MICHAEL BRUIST; Fiscal Year: 1991
    ..The AIDS virus uses it to incorporate its genome into the chromosomes of immune cells. Immunoglobulin genes rearrange by site-specific recombination iii order to create the wide variety of antibodies available to ..
  50. CHARACTERIZATION AND EXPRESSION OF AN LG VH GENE FAMILY
    DAN SCHULZE; Fiscal Year: 1991
    Recently molecular approaches have demonstrated mechanisms involved in generation of diversity within immunoglobulin genes. These include the description of rearrangement of germ-line segments (variable-diversity-joining, V/H-D-J/H for ..
  51. Human TNFa-Induced Pre-B Cell Bone Marrow Emigrants
    MARC LEVESQUE; Fiscal Year: 2007
    ..that expand in colony forming assays, and subpopulations that express AID and have somatically mutated immunoglobulin genes despite their development outside germinal centers...
  52. Regulation of the E. coli Y-family polymearse DinB
    JAMES FOTI; Fiscal Year: 2009
    ..requires the mutagenic potential of the Y-family of DNA polymerases to increase the mutation frequency in immunoglobulin genes. Mistargeted SHM decreases genomic stability and is thought to contribute to B-cell malignancies...
  53. Structural Insights Into Regulation of SOS Mutagenesis
    Martin Gonzalez; Fiscal Year: 2003
    ..may play a role in processes from cancer establishment to induction of somatic cell hypermutation of immunoglobulin genes. Therefore, DNA polV activity and regulation is an ideal model to study for two reasons: (i) the regulation ..
  54. Control of B Cell Development by Histone Methylation
    LANCE THOMAS; Fiscal Year: 2006
    ..To generate the antigen receptor repertoire that mediates mammalian immunity, lymphocytes must assemble immunoglobulin genes from separate coding segments via V(D)J recombination...
  55. MEETING ON MOLECULAR BASIS OF TUMOR IMMUNOLOGY
    Ellen Vitetta; Fiscal Year: 1990
    ..Recent studies of immunoglobulin genes, T-cell receptor genes, the processing of antigens, MHC genes, and T-lymphocytes have supported the ..
  56. MOLECULAR BASIS OF CELL GROWTH AND TRANSFORMATION
    Robert Roeder; Fiscal Year: 1999
    ..elaboration of the nature and mechanism of action of lymphoid specific factors implicated in activation of immunoglobulin genes (e.g. OCT2, BAF, NPkB, PU.1) and other stage- specific (e.g...
  57. ROLES OF DNA PK IN DNA DOUBLE STRAND BREAK REPAIR
    David Chen; Fiscal Year: 2001
    ..like ionizing radiation, but also for the dsb intermediated that are required for the rearrangement of immunoglobulin genes, i.e., V(D)J recombination. These three proteins are Ku70, Ku80 and DNAPKcs (460 kDa)...
  58. IMMUNOGLOBULIN GENES IN DIFFERENTIATING B CELLS
    Naomi Rosenberg; Fiscal Year: 1990
    ....
  59. ANTIBODY RESPONSE IN HUMANS TO PIG XENOANTIGENS
    DONALD CRAMER; Fiscal Year: 2001
    ..We intend identify the immunoglobulin genes that control the antibody response(s) mounted by patients exposed to pig tissues, isolate and characterize ..
  60. DEVELOPMENT OF RODENT MODELS FOR XENOTRANSPLANTATION
    DONALD CRAMER; Fiscal Year: 2001
    ..characteristics of the type of xenograft reaction observed; (2) establish the nature of the immunoglobulin genes and B cell subsets that control the humoral response to xenografts and whether this response is consistent ..
  61. ENGINEERING OF AN IMPROVED HUMAN FUSION PARTNER
    Michael Rosenberg; Fiscal Year: 1993
    ..yield stable clones with high antibody production following fusion and would not express its endogenous immunoglobulin genes.The goal of this proposed plan is to construct a superior fusion partner...
  62. ANALYSIS OF THE IMMUNOGLOBULIN HYPERMUTATOR MECHANISM
    Jay Short; Fiscal Year: 1992
    ..that can be utilized both in vivo and in vitro for rapidly monitoring hypersomatic mutation events within immunoglobulin genes. The availability of such an assay is essential for characterizing the antibody mutator activity and ..
  63. CELLULAR MECHANISMS IN THE IMMUNE RESPONSE
    Richard Dutton; Fiscal Year: 1992
    ..differentiation phase of the B cell response analysed with cells from transgenic mice expressing rearranged immunoglobulin genes with cells expressing the V-ese gene in the B cell response to High-SRBC. 4...