immunoglobulin genes


Summary: Genes and gene segments encoding the IMMUNOGLOBULIN LIGHT CHAINS. Gene segments of the light chain genes are designated as V (variable), J (joining), and C (constant).

Top Publications

  1. Robbiani D, Bunting S, Feldhahn N, Bothmer A, Camps J, Deroubaix S, et al. AID produces DNA double-strand breaks in non-Ig genes and mature B cell lymphomas with reciprocal chromosome translocations. Mol Cell. 2009;36:631-41 pubmed publisher
    ..We conclude that AID produces DSBs throughout the genome, which can lead to lymphoma-associated chromosome translocations in mature B cells...
  2. Dagklis A, Fazi C, Sala C, Cantarelli V, Scielzo C, Massacane R, et al. The immunoglobulin gene repertoire of low-count chronic lymphocytic leukemia (CLL)-like monoclonal B lymphocytosis is different from CLL: diagnostic implications for clinical monitoring. Blood. 2009;114:26-32 pubmed publisher
    ..Detailed IG analysis of individual MBL may help to identify cases that necessitate continuous clinical monitoring to anticipate disease progression...
  3. Yan C, Boboila C, Souza E, Franco S, Hickernell T, Murphy M, et al. IgH class switching and translocations use a robust non-classical end-joining pathway. Nature. 2007;449:478-82 pubmed
    ..In the absence of C-NHEJ, this alternative end-joining pathway also frequently joins Igh locus breaks to other chromosomes to generate translocations...
  4. Lim A, Luderschmidt S, Weidinger A, Schnopp C, Ring J, Hein R, et al. The IgE repertoire in PBMCs of atopic patients is characterized by individual rearrangements without variable region of the heavy immunoglobulin chain bias. J Allergy Clin Immunol. 2007;120:696-706 pubmed
    ..The detailed analysis of the IgE B-cell repertoire is highly suitable to follow changes in IgE uses during different therapy modalities. ..
  5. Arakawa H. Immunoglobulin gene conversion and hypermutation assay by FACs. Subcell Biochem. 2006;40:351-2 pubmed
    ..To minimize the fluctuation of gene conversion or hypermutation events, it is needed to analyze many subclones of the DT40 mutant for calculating average sIgM (-) or (+) percentage. ..
  6. Gaëta B, Malming H, Jackson K, Bain M, Wilson P, Collins A. iHMMune-align: hidden Markov model-based alignment and identification of germline genes in rearranged immunoglobulin gene sequences. Bioinformatics. 2007;23:1580-7 pubmed
    ..iHMMune-align cross-platform Java executable and web interface are freely available to academic users and can be accessed at ..
  7. Kobrin C, Cha S, Qin H, Raffeld M, Fend F, Quintanilla Martinez L, et al. Molecular analysis of light-chain switch and acute lymphoblastic leukemia transformation in two follicular lymphomas: implications for lymphomagenesis. Leuk Lymphoma. 2006;47:1523-34 pubmed
    ..It is also possible that the outgrowth of these variants was a consequence of immunoselection. ..
  8. Brown G, Kaattari I, Kaattari S. Two new Ig VH gene families in Oncorhynchus mykiss. Immunogenetics. 2006;58:933-6 pubmed publisher
  9. Blagodatski A, Batrak V, Schmidl S, Schoetz U, Caldwell R, Arakawa H, et al. A cis-acting diversification activator both necessary and sufficient for AID-mediated hypermutation. PLoS Genet. 2009;5:e1000332 pubmed publisher
    ..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. ..

More Information


  1. Lefranc M, Giudicelli V, Ginestoux C, Jabado Michaloud J, Folch G, Bellahcene F, et al. IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res. 2009;37:D1006-12 pubmed publisher
    ..IMGT is freely available at ..
  2. Rawstron A, Bennett F, O Connor S, Kwok M, Fenton J, Plummer M, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359:575-83 pubmed publisher
    ..Asymptomatic persons with fewer CLL-phenotype cells have monoclonal B-cell lymphocytosis (MBL). The goal of this study was to investigate the relation between MBL and CLL...
  3. Di Noia J, Neuberger M. Molecular mechanisms of antibody somatic hypermutation. Annu Rev Biochem. 2007;76:1-22 pubmed
    ..AID-triggered DNA deamination also underpins immunoglobulin variable (IgV) gene conversion, isotype class switching, and some oncogenic translocations in B cell tumors. ..
  4. Yang S, Fugmann S, Schatz D. Control of gene conversion and somatic hypermutation by immunoglobulin promoter and enhancer sequences. J Exp Med. 2006;203:2919-28 pubmed
    ..Our results indicate that cis-acting elements are important for Ig gene diversification, and we propose that targeting specificity is achieved through the combined action of several Ig locus elements that include the promoter. ..
  5. Bengten E, Quiniou S, Hikima J, Waldbieser G, Warr G, Miller N, et al. Structure of the catfish IGH locus: analysis of the region including the single functional IGHM gene. Immunogenetics. 2006;58:831-44 pubmed
    ..4-kb block of VH genes has occurred. These observations suggest that the IGH locus of teleost fish varies significantly from species to species in the diversity of C-region genes as well as the numbers of genes encoding V regions...
  6. Andréasson U, Flicker S, Lindstedt M, Valenta R, Greiff L, Korsgren M, et al. The human IgE-encoding transcriptome to assess antibody repertoires and repertoire evolution. J Mol Biol. 2006;362:212-27 pubmed
  7. Herzog S, Hug E, Meixlsperger S, Paik J, Depinho R, Reth M, et al. SLP-65 regulates immunoglobulin light chain gene recombination through the PI(3)K-PKB-Foxo pathway. Nat Immunol. 2008;9:623-31 pubmed publisher
    ..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. ..
  8. Bao Y, Wang T, Guo Y, Zhao Z, Li N, Zhao Y. The immunoglobulin gene loci in the teleost Gasterosteus aculeatus. Fish Shellfish Immunol. 2010;28:40-8 pubmed publisher
  9. VELA J, Ait Azzouzene D, Duong B, Ota T, Nemazee D. Rearrangement of mouse immunoglobulin kappa deleting element recombining sequence promotes immune tolerance and lambda B cell production. Immunity. 2008;28:161-70 pubmed publisher
    ..These results provide insight into the mechanism of L chain isotype exclusion and indicate that RS has a physiological role in promoting the formation of lambda L chain-expressing B cells. ..
  10. Masuda K, Ouchida R, Hikida M, Kurosaki T, Yokoi M, Masutani C, et al. DNA polymerases eta and theta function in the same genetic pathway to generate mutations at A/T during somatic hypermutation of Ig genes. J Biol Chem. 2007;282:17387-94 pubmed
    ..These results reveal genetic and biochemical interactions between POLH and POLQ and suggest that POLQ might cooperate with POLH to generate some of the A/T mutations during the somatic hypermutation of Ig genes. ..
  11. Das S, Nozawa M, Klein J, Nei M. Evolutionary dynamics of the immunoglobulin heavy chain variable region genes in vertebrates. Immunogenetics. 2008;60:47-55 pubmed publisher
    ..Our results suggest that the evolution of IGHV multigene family is more complex than previously thought and that several factors may act synergistically for the development of antibody repertoire. ..
  12. Lefranc M. WHO-IUIS Nomenclature Subcommittee for immunoglobulins and T cell receptors report August 2007, 13th International Congress of Immunology, Rio de Janeiro, Brazil. Dev Comp Immunol. 2008;32:461-3 pubmed
  13. Robbiani D, Bothmer A, Callen E, Reina San Martin B, Dorsett Y, Difilippantonio S, et al. AID is required for the chromosomal breaks in c-myc that lead to c-myc/IgH translocations. Cell. 2008;135:1028-38 pubmed publisher
    ..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. ..
  14. Zhang Z, Espinoza C, Yu Z, Stephan R, He T, Williams G, et al. Transcription factor Pax5 (BSAP) transactivates the RAG-mediated V(H)-to-DJ(H) rearrangement of immunoglobulin genes. Nat Immunol. 2006;7:616-24 pubmed
    ..These findings indicate a direct activating function for Pax5 in RAG-mediated immunoglobulin V(H)-to-DJ(H) recombination. ..
  15. Li Z, Luo Z, Ronai D, Kuang F, Peled J, Iglesias Ussel M, et al. Targeting AID to the Ig genes. Adv Exp Med Biol. 2007;596:93-109 pubmed
  16. Wang J, Alt F, Gostissa M, Datta A, Murphy M, Alimzhanov M, et al. Oncogenic transformation in the absence of Xrcc4 targets peripheral B cells that have undergone editing and switching. J Exp Med. 2008;205:3079-90 pubmed publisher
    ..Thus, Xrcc4/p53-deficient pro-B lymphomas routinely activate c-myc by gene amplification, whereas Xrcc4/p53-deficient peripheral B cell lymphomas routinely ectopically activate a single c-myc copy...
  17. Saberi A, Nakahara M, Sale J, Kikuchi K, Arakawa H, Buerstedde J, et al. The 9-1-1 DNA clamp is required for immunoglobulin gene conversion. Mol Cell Biol. 2008;28:6113-22 pubmed publisher
    ..This suggests that the roles of Rad9 and Rad17 may be confined to a subset of homologous recombination reactions initiated by replication-stalling lesions rather than those associated with double-strand break repair...
  18. Janz S. Myc translocations in B cell and plasma cell neoplasms. DNA Repair (Amst). 2006;5:1213-24 pubmed
    ..Transgenic mouse models of T(12;15)/t(8;14), including newly developed "iMyc" gene-insertion mice, will be useful in elucidating the role of these CSR factors in the progression of Myc-induced B cell tumors. ..
  19. Chen L, Li M, Li Q, Yang X, An X, Chen Y. Characterization of the bovine immunoglobulin lambda light chain constant IGLC genes. Vet Immunol Immunopathol. 2008;124:284-94 pubmed publisher
    ..Phylogenetic analysis indicated that the bovine IGLC genes were more closely related to their equivalents in sheep and goats than that to other mammals. ..
  20. Kovalchuk A, DuBois W, Mushinski E, McNeil N, Hirt C, Qi C, et al. AID-deficient Bcl-xL transgenic mice develop delayed atypical plasma cell tumors with unusual Ig/Myc chromosomal rearrangements. J Exp Med. 2007;204:2989-3001 pubmed
    ..In contrast, the second was T(12;15) negative, but had an elevated N-Myc expression caused by a paracentric inversion of chromosome 12. Thus, novel mechanisms juxtapose Ig and Myc-family genes in AID-deficient plasma cell tumors. ..
  21. Xu C, Feeney A. The epigenetic profile of Ig genes is dynamically regulated during B cell differentiation and is modulated by pre-B cell receptor signaling. J Immunol. 2009;182:1362-9 pubmed
    ..Our data indicate that the epigenetic profile of IgL genes is dramatically modulated by pre-BCR signaling and B cell differentiation status. ..
  22. Kitao H, Kimura M, Yamamoto K, Seo H, Namikoshi K, Agata Y, et al. Regulation of histone H4 acetylation by transcription factor E2A in Ig gene conversion. Int Immunol. 2008;20:277-84 pubmed publisher
    ..Thus, E2A may contribute to GCV by maintaining histone acetylation, which could be a prerequisite for targeting or full deaminase function of AID. ..
  23. Wang J, Gostissa M, Yan C, Goff P, Hickernell T, Hansen E, et al. Mechanisms promoting translocations in editing and switching peripheral B cells. Nature. 2009;460:231-6 pubmed publisher
    ..Our studies show peripheral B cells that attempt secondary V(D)J recombination, and determine a role for mechanistic factors in promoting recurrent translocations in tumours...
  24. Liu Y, Li L, Kumar K, Xie C, Lightfoot S, Zhou X, et al. Lupus susceptibility genes may breach tolerance to DNA by impairing receptor editing of nuclear antigen-reactive B cells. J Immunol. 2007;179:1340-52 pubmed
    ..Taken together with a recent report on Sle1(z), these studies suggest that dysregulated receptor-editing of nuclear Ag-reactive B cells may be a major mechanism through which antinuclear Abs arise in lupus. ..
  25. Bleakley K, Lefranc M, Biau G. Recovering probabilities for nucleotide trimming processes for T cell receptor TRA and TRG V-J junctions analyzed with IMGT tools. BMC Bioinformatics. 2008;9:408 pubmed publisher
    ..With increasing high-throughput of standardized immunogenetics data, similar probabilistic approaches will improve understanding of processes so far only characterized by the "output" of standardized tools. ..
  26. Volkheimer A, Weinberg J, Beasley B, Whitesides J, Gockerman J, Moore J, et al. Progressive immunoglobulin gene mutations in chronic lymphocytic leukemia: evidence for antigen-driven intraclonal diversification. Blood. 2007;109:1559-67 pubmed
    Somatic mutations of immunoglobulin genes characterize mature memory B cells, and intraclonal B-cell diversification is typically associated with expansion of B-cell clones with greater affinity for antigen (antigen drive)...
  27. Tang E, Martin A. NHEJ-deficient DT40 cells have increased levels of immunoglobulin gene conversion: evidence for a double strand break intermediate. Nucleic Acids Res. 2006;34:6345-51 pubmed
    ..These data suggest that a DSB is the major DNA lesion that initiates GC. ..
  28. Giudicelli V, Chaume D, Lefranc M. IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res. 2005;33:D256-61 pubmed
    ..IMGT/GENE-DB is freely available at ..
  29. Jackson K, Gaeta B, Sewell W, Collins A. Exonuclease activity and P nucleotide addition in the generation of the expressed immunoglobulin repertoire. BMC Immunol. 2004;5:19 pubmed
    ..The study of such processes has been compromised by difficulties in reliably aligning immunoglobulin genes and in the partitioning of nucleotides between segment ends, and between N and P nucleotides...
  30. Solem S, Stenvik J. Antibody repertoire development in teleosts--a review with emphasis on salmonids and Gadus morhua L. Dev Comp Immunol. 2006;30:57-76 pubmed
    ..Information on the establishment of the preimmune repertoire, and the possible role of environmental antigens is also sparse. ..
  31. Sayegh C, Sayegh C, Jhunjhunwala S, Riblet R, Murre C. Visualization of looping involving the immunoglobulin heavy-chain locus in developing B cells. Genes Dev. 2005;19:322-7 pubmed
    ..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. ..
  32. Baum T, Hierle V, Pasqual N, Bellahcene F, Chaume D, Lefranc M, et al. IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give access to all TR potential V(D)J recombinations. BMC Bioinformatics. 2006;7:224 pubmed
    ..This is useful for biologists and bioinformaticians for the study of T lymphocyte V(D)J gene rearrangements and their applications in immune response analysis. ..
  33. Ghia P, Stamatopoulos K, Belessi C, Moreno C, Stella S, Guida G, et al. Geographic patterns and pathogenetic implications of IGHV gene usage in chronic lymphocytic leukemia: the lesson of the IGHV3-21 gene. Blood. 2005;105:1678-85 pubmed
    ..The second subset may reflect the physiologic heterogeneity of expression of IGHV3-21 rearrangements in the normal repertoire and is characterized by a variable clinical outcome. ..
  34. Parsa J, Basit W, Wang C, Gommerman J, Carlyle J, Martin A. AID mutates a non-immunoglobulin transgene independent of chromosomal position. Mol Immunol. 2007;44:567-75 pubmed
  35. Schatz D, Spanopoulou E. Biochemistry of V(D)J recombination. Curr Top Microbiol Immunol. 2005;290:49-85 pubmed
    ..We discuss how the RAG proteins interact with DNA and how coordinate cleavage of the DNA at two sites might be achieved. Finally, we consider the RAG proteins and V(D)J recombination from an evolutionary point of view. ..
  36. Ramiro A, Jankovic M, Callen E, Difilippantonio S, Chen H, McBride K, et al. Role of genomic instability and p53 in AID-induced c-myc-Igh translocations. Nature. 2006;440:105-9 pubmed
    ..Our findings reveal a pathway for surveillance and protection against AID-dependent DNA damage, leading to chromosomal translocations. ..
  37. Saribasak H, Saribasak N, Ipek F, Ellwart J, Arakawa H, Buerstedde J. Uracil DNA glycosylase disruption blocks Ig gene conversion and induces transition mutations. J Immunol. 2006;176:365-71 pubmed
    ..This suggests that hypermutating B cells process activation-induced cytidine deaminase-induced uracils with approximately one-seventh of uracils giving rise to mutations depending on their position. ..
  38. Jones J, Ghaffari S, Lobb C. Patterns of gene divergence and VL promoter activity in immunoglobulin light chain clusters of the channel catfish. Immunogenetics. 2004;56:448-61 pubmed
    ..These results indicate that the structure and function of VL promoter regions in the regulation and tissue specificity of L-chain gene expression evolved early in phylogeny. ..
  39. Lefranc M, Giudicelli V, Kaas Q, Duprat E, Jabado Michaloud J, Scaviner D, et al. IMGT, the international ImMunoGeneTics information system. Nucleic Acids Res. 2005;33:D593-7 pubmed
    ..IMGT is freely available at ..
  40. Kuppers R. Mechanisms of B-cell lymphoma pathogenesis. Nat Rev Cancer. 2005;5:251-62 pubmed
    ..Recent insights into the lymphomagenic role of factors supplied by the microenvironment also offer new therapeutic strategies. ..
  41. Ratcliffe M. Antibodies, immunoglobulin genes and the bursa of Fabricius in chicken B cell development. Dev Comp Immunol. 2006;30:101-18 pubmed
    ..This review focuses on the differences between B cell development in the chicken as compared to rodent and primate models...
  42. Delbos F, De Smet A, Faili A, Aoufouchi S, Weill J, Reynaud C. Contribution of DNA polymerase eta to immunoglobulin gene hypermutation in the mouse. J Exp Med. 2005;201:1191-6 pubmed
    The mutation pattern of immunoglobulin genes was studied in mice deficient for DNA polymerase eta, a translesional polymerase whose inactivation is responsible for the xeroderma pigmentosum variant (XP-V) syndrome in humans...
  43. Hansen J, Landis E, Phillips R. Discovery of a unique Ig heavy-chain isotype (IgT) in rainbow trout: Implications for a distinctive B cell developmental pathway in teleost fish. Proc Natl Acad Sci U S A. 2005;102:6919-24 pubmed
    ..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. ..
  44. Schroeder H. Similarity and divergence in the development and expression of the mouse and human antibody repertoires. Dev Comp Immunol. 2006;30:119-35 pubmed
  45. Jung D, Giallourakis C, Mostoslavsky R, Alt F. Mechanism and control of V(D)J recombination at the immunoglobulin heavy chain locus. Annu Rev Immunol. 2006;24:541-70 pubmed
    ..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. ..
  46. Giudicelli V, Duroux P, Ginestoux C, Folch G, Jabado Michaloud J, Chaume D, et al. IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic Acids Res. 2006;34:D781-4 pubmed
    ..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 ..
  47. Schelonka R, Ivanov I, Jung D, Ippolito G, Nitschke L, Zhuang Y, et al. A single DH gene segment creates its own unique CDR-H3 repertoire and is sufficient for B cell development and immune function. J Immunol. 2005;175:6624-32 pubmed
    ..Although limited to a repertoire specific to DFL16.1, the presence of a single DH gene segment of normal sequence was sufficient for development of normal numbers of mature B cells and for robust humoral immune function. ..
  48. Masuda K, Ouchida R, Takeuchi A, Saito T, Koseki H, Kawamura K, et al. DNA polymerase theta contributes to the generation of C/G mutations during somatic hypermutation of Ig genes. Proc Natl Acad Sci U S A. 2005;102:13986-91 pubmed
  49. Danilova N, Bussmann J, Jekosch K, Steiner L. The immunoglobulin heavy-chain locus in zebrafish: identification and expression of a previously unknown isotype, immunoglobulin Z. Nat Immunol. 2005;6:295-302 pubmed
    ..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. ..
  50. Stanton M, Brodeur P. Stat5 mediates the IL-7-induced accessibility of a representative D-Distal VH gene. J Immunol. 2005;174:3164-8 pubmed
    ..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. ..
  51. Barreto V, Ramiro A, Nussenzweig M. Activation-induced deaminase: controversies and open questions. Trends Immunol. 2005;26:90-6 pubmed
  52. Lefranc M, Clement O, Kaas Q, Duprat E, Chastellan P, Coelho I, et al. IMGT-Choreography for immunogenetics and immunoinformatics. In Silico Biol. 2005;5:45-60 pubmed
    ..IMGT is freely available at ..
  53. Hsu E, Pulham N, Rumfelt L, Flajnik M. The plasticity of immunoglobulin gene systems in evolution. Immunol Rev. 2006;210:8-26 pubmed