immunoglobulin joining region

Summary

Summary: A segment of the immunoglobulin heavy chains, encoded by the IMMUNOGLOBULIN HEAVY CHAIN GENES in the J segment where, during the maturation of B-LYMPHOCYTES; the gene segment for the variable region upstream is joined to a constant region gene segment downstream. The exact position of joining of the two gene segments is variable and contributes to ANTIBODY DIVERSITY. It is distinguished from the IMMUNOGLOBULIN J CHAINS; a separate polypeptide that serves as a linkage piece in polymeric IGA or IGM.

Top Publications

  1. Pan P, Lieber M, Teale J. The role of recombination signal sequences in the preferential joining by deletion in DH-JH recombination and in the ordered rearrangement of the IgH locus. Int Immunol. 1997;9:515-22 pubmed
    ..Therefore, if all three segments were accessible, RSS/coding end effects would not contribute to the ordered rearrangement of the IgH locus. ..
  2. Nitschke L, Kestler J, Tallone T, Pelkonen S, Pelkonen J. Deletion of the DQ52 element within the Ig heavy chain locus leads to a selective reduction in VDJ recombination and altered D gene usage. J Immunol. 2001;166:2540-52 pubmed
    ..We propose a model in which the DQ52 promoter region enhances the induction of secondary DJ rearrangements. ..
  3. Reynaud C, Dahan A, Anquez V, Weill J. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region. Cell. 1989;59:171-83 pubmed
    ..Allelic exclusion appears to be performed by restriction of a complete VDJ rearrangement to a single allele. ..
  4. Kawasaki K, Minoshima S, Nakato E, Shibuya K, Shintani A, Schmeits J, et al. One-megabase sequence analysis of the human immunoglobulin lambda gene locus. Genome Res. 1997;7:250-61 pubmed
    ..Sequence organization suggests that large DNA duplications diversified the germ-line repertoire of the V lambda gene segments. ..
  5. Haire R, Rast J, Litman R, Litman G. Characterization of three isotypes of immunoglobulin light chains and T-cell antigen receptor alpha in zebrafish. Immunogenetics. 2000;51:915-23 pubmed
    ..The gene sequences reported provide an essential set of markers of both B- and T-cell lineages that will facilitate investigations of immune system development. ..
  6. Ivanov I, Schelonka R, Zhuang Y, Gartland G, Zemlin M, Schroeder H. Development of the expressed Ig CDR-H3 repertoire is marked by focusing of constraints in length, amino acid use, and charge that are first established in early B cell progenitors. J Immunol. 2005;174:7773-80 pubmed
    ..08 +/- 0.03) to mild hydrophilic in fraction F (-0.17 +/- 0.02). Fundamental constraints on the sequence and structure of CDR-H3 are thus established before surface IgM expression. ..
  7. Pelanda R, Schwers S, Sonoda E, Torres R, Nemazee D, Rajewsky K. Receptor editing in a transgenic mouse model: site, efficiency, and role in B cell tolerance and antibody diversification. Immunity. 1997;7:765-75 pubmed
  8. Chen J, Trounstine M, Alt F, Young F, Kurahara C, Loring J, et al. Immunoglobulin gene rearrangement in B cell deficient mice generated by targeted deletion of the JH locus. Int Immunol. 1993;5:647-56 pubmed
    ..Expression of mu chains may facilitate either efficient L chain gene rearrangement or the survival of cells that have rearranged light chain genes by promoting the differentiation of large, CD43+ to small, CD43- pre-B cells. ..
  9. Ohm Laursen L, Nielsen M, Larsen S, Barington T. No evidence for the use of DIR, D-D fusions, chromosome 15 open reading frames or VH replacement in the peripheral repertoire was found on application of an improved algorithm, JointML, to 6329 human immunoglobulin H rearrangements. Immunology. 2006;119:265-77 pubmed
    ..An online version 1.0 of JointML is available at http://www.cbs.dtu.dk/services/VDJsolver. ..

More Information

Publications62

  1. Li Z, Dordai D, Lee J, Desiderio S. A conserved degradation signal regulates RAG-2 accumulation during cell division and links V(D)J recombination to the cell cycle. Immunity. 1996;5:575-89 pubmed
    ..Using transgenic mice expressing the T490A RAG-2 mutant and a functional T cell receptor beta chain, we demonstrate that coupling of V(D)J recombination to the cell cycle is not essential for enforcement of allelic exclusion. ..
  2. Wu L, Liu Y, Strandtmann J, Mak C, Lee B, Li Z, et al. The mouse DNA binding protein Rc for the kappa B motif of transcription and for the V(D)J recombination signal sequences contains composite DNA-protein interaction domains and belongs to a new family of large transcriptional proteins. Genomics. 1996;35:415-24 pubmed
    ..The major histocompatibility complex class I gene enhancer binding proteins MBP1 and MBP2 are other representatives of this ZAS protein family. ..
  3. Pelanda R, Schaal S, Torres R, Rajewsky K. A prematurely expressed Ig(kappa) transgene, but not V(kappa)J(kappa) gene segment targeted into the Ig(kappa) locus, can rescue B cell development in lambda5-deficient mice. Immunity. 1996;5:229-39 pubmed
  4. Erlandsson L, Andersson K, Sigvardsson M, Lycke N, Leanderson T. Mice with an inactivated joining chain locus have perturbed IgM secretion. Eur J Immunol. 1998;28:2355-65 pubmed
    ..Finally, after immunization with T-dependent or T-independent antigens the IgM component of the immune response was reduced in J-/- mice while only a marginal reduction of the IgG response was detected. ..
  5. Chang Y, Bosma G, Bosma M. Development of B cells in scid mice with immunoglobulin transgenes: implications for the control of V(D)J recombination. Immunity. 1995;2:607-16 pubmed
    ..This rescue of scid B cell differentiation is associated with a dramatic reduction in expression of the recombination activation genes, RAG1 and RAG2, and with reduced transcription of the kappa locus. ..
  6. Yousfi Monod M, Giudicelli V, Chaume D, Lefranc M. IMGT/JunctionAnalysis: the first tool for the analysis of the immunoglobulin and T cell receptor complex V-J and V-D-J JUNCTIONs. Bioinformatics. 2004;20 Suppl 1:i379-85 pubmed
    ..IMGT/JunctionAnalysis is available from the IMGT Home page at http://imgt.cines.fr ..
  7. Takagaki Y, Nakanishi N, Ishida I, Kanagawa O, Tonegawa S. T cell receptor-gamma and -delta genes preferentially utilized by adult thymocytes for the surface expression. J Immunol. 1989;142:2112-21 pubmed
    ..Inasmuch as this gene was not expressed in BW5147 cells or in fetal thymocyte hybridomas expressing V5 or V6 gamma genes, there exists a novel V gene segment-dependent control of transcription in the gamma-gene system. ..
  8. Hesse J, Lieber M, Mizuuchi K, Gellert M. V(D)J recombination: a functional definition of the joining signals. Genes Dev. 1989;3:1053-61 pubmed
    ..Although the two signal types share sequence motifs, we find no evidence of a role in recombination for homology between the signals, suggesting that they serve primarily as protein recognition and binding sites. ..
  9. Sadofsky M. The RAG proteins in V(D)J recombination: more than just a nuclease. Nucleic Acids Res. 2001;29:1399-409 pubmed
    ..Two proteins, RAG1 and RAG2, together form the nuclease that cleaves the DNA at the border of the signal sequences. Additional roles of these proteins in organizing the reaction complex for subsequent steps are explored. ..
  10. Talukder S, Dudley D, Alt F, Takahama Y, Akamatsu Y. Increased frequency of aberrant V(D)J recombination products in core RAG-expressing mice. Nucleic Acids Res. 2004;32:4539-49 pubmed
    ..We provide the first evidence that the non-core regions of RAGs have critical functions in the proper assembly and resolution of recombination intermediates in endogenous antigen receptor loci. ..
  11. Souto Carneiro M, Longo N, Russ D, Sun H, Lipsky P. Characterization of the human Ig heavy chain antigen binding complementarity determining region 3 using a newly developed software algorithm, JOINSOLVER. J Immunol. 2004;172:6790-802 pubmed
    ..Analysis of the human CDR3(H) with JOINSOLVER has provided comprehensive information on the influences that shape this important Ag binding region of V(H) chains. ..
  12. Han S, Dillon S, Zheng B, Shimoda M, Schlissel M, Kelsoe G. V(D)J recombinase activity in a subset of germinal center B lymphocytes. Science. 1997;278:301-5 pubmed
    ..This restriction preserves efficient antigen-driven selection in germinal centers while allowing for saltations in the somatic evolution of B cells. ..
  13. Petiniot L, Weaver Z, Barlow C, Shen R, Eckhaus M, Steinberg S, et al. Recombinase-activating gene (RAG) 2-mediated V(D)J recombination is not essential for tumorigenesis in Atm-deficient mice. Proc Natl Acad Sci U S A. 2000;97:6664-9 pubmed
    ..Furthermore, these data suggest that V(D)J recombination is a critical, but not essential, event during which Atm-deficient thymocytes are susceptible to developing chromosome aberrations that predispose to malignant transformation. ..
  14. Giudicelli V, Chaume D, Lefranc M. IMGT/V-QUEST, an integrated software program for immunoglobulin and T cell receptor V-J and V-D-J rearrangement analysis. Nucleic Acids Res. 2004;32:W435-40 pubmed
    ..IMGT/V-QUEST is currently available for human and mouse, and partly for non-human primates, sheep, chondrichthyes and teleostei. IMGT/V-QUEST is freely available at http://imgt.cines.fr. ..
  15. Bories J, Demengeot J, Davidson L, Alt F. Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility. Proc Natl Acad Sci U S A. 1996;93:7871-6 pubmed
    ..These results demonstrate a critical role for Ebeta in promoting accessibility of the TCRbeta locus and suggest that additional negative elements may cooperate to further modulate this process. ..
  16. 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...
  17. Jakobovits A, Vergara G, Kennedy J, Hales J, McGuinness R, Casentini Borocz D, et al. Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production. Proc Natl Acad Sci U S A. 1993;90:2551-5 pubmed
    ..This novel B-cell-deficient mouse strain provides a tool for studying the recombination and expression of exogenous immunoglobulin genes introduced into the mouse germ line. ..
  18. Gilfillan S, Dierich A, LeMeur M, Benoist C, Mathis D. Mice lacking TdT: mature animals with an immature lymphocyte repertoire. Science. 1993;261:1175-8 pubmed
    ..Thus, switch-on of the TdT gene during the first week after birth provokes an even greater expansion of lymphocyte receptor diversity than had previously been thought. ..
  19. Ramsden D, Gellert M. Formation and resolution of double-strand break intermediates in V(D)J rearrangement. Genes Dev. 1995;9:2409-20 pubmed
    ..Efficient formation of signal junctions may require cell cycle progression, or down-regulation of the recombination machinery. ..
  20. Brochet X, Lefranc M, Giudicelli V. IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis. Nucleic Acids Res. 2008;36:W503-8 pubmed publisher
    ..The 'Advanced parameters' allow to modify default parameters used by IMGT/V-QUEST and IMGT/JunctionAnalysis according to the users' interest. IMGT/V-QUEST is freely available for academic research at http://imgt.cines.fr. ..
  21. Hewitt S, Chaumeil J, Skok J. Chromosome dynamics and the regulation of V(D)J recombination. Immunol Rev. 2010;237:43-54 pubmed publisher
  22. Gu Y, Jin S, Gao Y, Weaver D, Alt F. Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination. Proc Natl Acad Sci U S A. 1997;94:8076-81 pubmed
    ..Potential differences between the Ku70(-/-) and Ku80(-/-) V(D)J recombination defects are discussed. ..
  23. 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. ..
  24. Komori T, Okada A, Stewart V, Alt F. Lack of N regions in antigen receptor variable region genes of TdT-deficient lymphocytes. Science. 1993;261:1171-5 pubmed
  25. Osipovich O, Milley R, Meade A, Tachibana M, Shinkai Y, Krangel M, et al. Targeted inhibition of V(D)J recombination by a histone methyltransferase. Nat Immunol. 2004;5:309-16 pubmed
    ..These findings indicate a key function for histone methyltransferases in the tissue- and stage-specific suppression of antigen receptor gene assembly during lymphocyte development. ..
  26. Nutt S, Thevenin C, Busslinger M. Essential functions of Pax-5 (BSAP) in pro-B cell development. Immunobiology. 1997;198:227-35 pubmed
    ..Together these data demonstrate therefore that B cell development in the Pax-5 deficient bone marrow is arrested at an early pro-B cell stage which is not yet responsive to pre-B cell receptor signaling. ..
  27. Montalbano A, Ogwaro K, Tang A, Matthews A, Larijani M, Oettinger M, et al. V(D)J recombination frequencies can be profoundly affected by changes in the spacer sequence. J Immunol. 2003;171:5296-304 pubmed
    ..These data demonstrate that the spacer sequence should be considered to play an important role in the recombination efficacy of an RSS, and that the effect of the spacer occurs primarily subsequent to RAG binding. ..
  28. Fang T, Smith B, Roman C. Conventional and surrogate light chains differentially regulate Ig mu and Dmu heavy chain maturation and surface expression. J Immunol. 2001;167:3846-57 pubmed
    ..These results establish a novel function of lambda5 in limiting surface pre-BCR levels and reveal biochemical properties of Ig molecules that may underlie the diverse consequences of pre-BCR signaling in vivo by different HCs. ..
  29. Knapp G, Setzer R, Fuscoe J. Quantitation of aberrant interlocus T-cell receptor rearrangements in mouse thymocytes and the effect of the herbicide 2,4-dichlorophenoxyacetic acid. Environ Mol Mutagen. 2003;42:37-43 pubmed
    ..No significant increase in aberrant V(D)J rearrangements was found, indicating that under these conditions 2,4-D does not appear to effect this important mechanism of carcinogenesis. ..
  30. Boursier L, Su W, Spencer J. Imprint of somatic hypermutation differs in human immunoglobulin heavy and lambda chain variable gene segments. Mol Immunol. 2003;39:1025-34 pubmed
    ..These observations suggest that some aspect of the mechanism of somatic hypermutation operates differently in human immunoglobulin heavy and lambda light chain variable gene segments. ..
  31. Neuberger M. Expression and regulation of immunoglobulin heavy chain gene transfected into lymphoid cells. EMBO J. 1983;2:1373-8 pubmed
    ..This segment, located between JH and switch regions, functioned both downstream of the VH exon and upstream in either orientation. The existence of a transcription enhancer element in this region is therefore proposed. ..
  32. Morbach H, Richl P, Faber C, Singh S, Girschick H. The kappa immunoglobulin light chain repertoire of peripheral blood B cells in patients with juvenile rheumatoid arthritis. Mol Immunol. 2008;45:3840-6 pubmed publisher
    ..Thus, B cell tolerance might be broken by more than one pathogenic mechanism. ..
  33. Briney B, Willis J, Crowe J. Human peripheral blood antibodies with long HCDR3s are established primarily at original recombination using a limited subset of germline genes. PLoS ONE. 2012;7:e36750 pubmed publisher
  34. Gozalbo López B, Andrade P, Terrados G, de Andres B, Serrano N, Cortegano I, et al. A role for DNA polymerase mu in the emerging DJH rearrangements of the postgastrulation mouse embryo. Mol Cell Biol. 2009;29:1266-75 pubmed publisher
  35. Takahashi T, Iwase T, Tachibana T, Komiyama K, Kobayashi K, Chen C, et al. Cloning and expression of the chicken immunoglobulin joining (J)-chain cDNA. Immunogenetics. 2000;51:85-91 pubmed
    ..These data indicated that the chicken J-chain gene displays a high degree of homology with that of other species, and is expressed at an early stage of development of the chicken immune system. ..
  36. Libra M, De Re V, Gasparotto D, Gloghini A, Marzotto A, Milan I, et al. Differentiation between non-Hodgkin's lymphoma recurrence and second primary lymphoma by VDJ rearrangement analysis. Br J Haematol. 2002;118:809-12 pubmed
    ..In contrast, primary and secondary tumours in two patients were of different clonal origin. Our data indicate that VDJ analysis is a fundamental tool for identification of relapses in NHL. ..
  37. Daubenberger C, Salomon M, Vecino W, H bner B, Troll H, Rodriques R, et al. Functional and structural similarity of V gamma 9V delta 2 T cells in humans and Aotus monkeys, a primate infection model for Plasmodium falciparum malaria. J Immunol. 2001;167:6421-30 pubmed
    ..The structural and functional conservation of Vgamma9Vdelta2 T cells in A. nancymaae and humans implicates a functionally important and evolutionary conserved mechanism of recognition of phosphorylated microbial metabolites...
  38. Kelsoe G. Studies of the humoral immune response. Immunol Res. 2000;22:199-210 pubmed
    ..I hope that my colleagues can accept this translucence and know that their efforts are recognized and deeply appreciated, nonetheless. ..
  39. Sonntag D, Weingartner B, Grutzmann R. A member of a novel human DH gene family: DHFL16. Nucleic Acids Res. 1989;17:1267 pubmed
  40. Gao Y, Chaudhuri J, Zhu C, Davidson L, Weaver D, Alt F. A targeted DNA-PKcs-null mutation reveals DNA-PK-independent functions for KU in V(D)J recombination. Immunity. 1998;9:367-76 pubmed
    ..Finally, while DNA-PK-null fibroblasts exhibited increased IR sensitivity, DNA-PKcs-deficient ES cells did not. We conclude that Ku70 and Ku80 may have functions in V(D)J recombination and DNA repair that are independent of DNA-PKcs. ..
  41. Sinclair M, Gilchrist J, Aitken R. Bovine IgG repertoire is dominated by a single diversified VH gene family. J Immunol. 1997;159:3883-9 pubmed
    ..Comparison of germline VH sequences with those gathered from adult bovine splenic cDNA demonstrates a pattern of nucleotide substitution that is consistent with diversification through somatic hypermutation. ..
  42. Nakayama K, Shinkai Y, Okumura K, Nakauchi H. Isolation and characterization of the mouse CD8 beta-chain (Ly-3) genes. Absence of an intervening sequence between V- and J-like gene segments. J Immunol. 1989;142:2540-6 pubmed
    ..1 and Ly-3.2 revealed a single base difference which results in an amino acid substitution. Therefore it is likely that this amino acid difference is responsible for the previously defined Ly-3 allotypes. ..
  43. Gerondakis S, Bernard O, Cory S, Adams J. Immunoglobulin JH rearrangement in a T-cell line reflects fusion to the DH locus at a sequence lacking the nonamer recognition signal. Immunogenetics. 1988;28:255-9 pubmed
    ..This result suggests that the heptamer may be the primary determinant of the specificity in V-gene assembly and that the DH locus as a whole may be preferred target for recombination. ..
  44. Baron B, Nucifora G, McCabe N, Espinosa R, Le Beau M, McKeithan T. Identification of the gene associated with the recurring chromosomal translocations t(3;14)(q27;q32) and t(3;22)(q27;q11) in B-cell lymphomas. Proc Natl Acad Sci U S A. 1993;90:5262-6 pubmed
    ..We propose the name BCL6 (B-cell lymphoma 6) for this gene, since it is likely to play a role in the pathogenesis of certain B-cell lymphomas. ..
  45. Kulkarni S, Sitaru C, Jakus Z, Anderson K, Damoulakis G, Davidson K, et al. PI3Kβ plays a critical role in neutrophil activation by immune complexes. Sci Signal. 2011;4:ra23 pubmed publisher
    ..These results define PI3Kβ as a potential therapeutic target in inflammatory disease. ..
  46. Lieber M, Hesse J, Mizuuchi K, Gellert M. Developmental stage specificity of the lymphoid V(D)J recombination activity. Genes Dev. 1987;1:751-61 pubmed
    ..No activity was found in several nonhematopoietic cell lines. Recombination was seen only among substrate molecules which had replicated in the eukaryotic cells. Several possible interpretations of this result are discussed. ..
  47. Huppi K, Siwarski D, Shaughnessy J, Klemsz M, Shirakata M, Maki R, et al. Genes associated with immunoglobulin V(D)J recombination are linked on mouse chromosome 2 and human chromosome 11. Immunogenetics. 1993;37:288-91 pubmed
  48. Muegge K. Modifications of histone cores and tails in V(D)J recombination. Genome Biol. 2003;4:211 pubmed
    ..A recent study shows that methylated lysine 79 in the core region of histone H3 also plays a role by providing a euchromatic 'mark' that may regulate access of the V(D)J recombinase. ..
  49. Lipsanen V, Walter B, Emara M, Siminovitch K, Lam J, Kaushik A. Restricted CDR3 length of the heavy chain is characteristic of six randomly isolated disease-associated VH J558+ IgM autoantibodies in lupus prone motheaten mice. Int Immunol. 1997;9:655-64 pubmed
    ..In addition, characteristic differences in the size and hydrophobicity pattern of the CDR3 of the heavy chain allow structural distinction between monospecific disease-associated IgM AAb and the polyreactive IgM NAAb. ..
  50. Evans M, Sanders J, Tagami T, Sanders P, Young S, Roberts E, et al. Monoclonal autoantibodies to the TSH receptor, one with stimulating activity and one with blocking activity, obtained from the same blood sample. Clin Endocrinol (Oxf). 2010;73:404-12 pubmed publisher
    ..Consequently, the two antibodies have evolved separately from different B cell clones. This study provides proof that a patient can produce a mixture of blocking and stimulating TSHR autoantibodies at the same time. ..
  51. Combriato G, Klobeck H. V lambda and J lambda-C lambda gene segments of the human immunoglobulin lambda light chain locus are separated by 14 kb and rearrange by a deletion mechanism. Eur J Immunol. 1991;21:1513-22 pubmed
    ..Sequences of 23 cDNA clones allow to establish a V lambda subgroup classification based on nucleic acid sequence data and an estimate of the J-C lambda usage. ..
  52. Stenvik J, Lundbäck A, Jørgensen T, Pilström L. Variable region diversity of the Atlantic cod (Gadus morhua L.) immunoglobulin heavy chain. Immunogenetics. 2000;51:670-80 pubmed
    ..On the other hand, the CDR3 length variability was restricted, and this may reduce the diversity of the cod VH region. ..
  53. Lebecque S, Gearhart P. Boundaries of somatic mutation in rearranged immunoglobulin genes: 5' boundary is near the promoter, and 3' boundary is approximately 1 kb from V(D)J gene. J Exp Med. 1990;172:1717-27 pubmed
    ..Rather, the data support a model for random point mutations where the mechanism is linked to the transcriptional state of the gene. ..