Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 Jul 1;182(1):109–119. doi: 10.1084/jem.182.1.109

Generation of immunoglobulin light chain gene diversity in Raja erinacea is not associated with somatic rearrangement, an exception to a central paradigm of B cell immunity

PMCID: PMC2192082  PMID: 7790811

Abstract

In all vertebrate species examined to date, rearrangement and somatic modification of gene segmental elements that encode portions of the antigen-combining sites of immunoglobulins are integral components of the generation of antibody diversity. In the phylogenetically primitive cartilaginous fishes, gene segments encoding immunoglobulin heavy and light chain loci are arranged in multiple clusters, in which segmental elements are separated by only 300-400 bp. In some cases, segmental elements are joined in the germline of nonlymphoid cells (joined genes). Both genomic library screening and direct amplification of genomic DNA have been used to characterize at least 89 different type I light chain gene clusters in the skate, Raja. Analyses of predicted nucleotide sequences and predicted peptide structures are consistent with the distribution of genes into different sequence groups. Predicted amino acid sequence differences are preferentially distributed in complementarity-determining versus framework regions, and replacement-type substitutions exceed neutral substitutions. When specific germline sequences are related to the sequences of individual cDNAs, it is apparent that the joined genes are expressed and are potentially somatically mutated. No evidence was found for the presence of any type I light chain gene in Raja that is not germline joined. The type I light chain gene clusters in Raja appear to represent a novel gene system in which combinatorial and junctional diversity are absent.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Boudinot P., Drapier A. M., Cazenave P. A., Sanchez P. Mechanistic and selective constraints act on the establishment of V lambda J lambda junctions in the B cell repertoire. J Immunol. 1994 Mar 1;152(5):2248–2255. [PubMed] [Google Scholar]
  2. Chou H. S., Nelson C. A., Godambe S. A., Chaplin D. D., Loh D. Y. Germline organization of the murine T cell receptor beta-chain genes. Science. 1987 Oct 23;238(4826):545–548. doi: 10.1126/science.2821625. [DOI] [PubMed] [Google Scholar]
  3. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  4. Greenberg A. S., Steiner L., Kasahara M., Flajnik M. F. Isolation of a shark immunoglobulin light chain cDNA clone encoding a protein resembling mammalian kappa light chains: implications for the evolution of light chains. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10603–10607. doi: 10.1073/pnas.90.22.10603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Greenhalgh P., Steiner L. A. Recombination activating gene 1 (Rag1) in zebrafish and shark. Immunogenetics. 1995;41(1):54–55. doi: 10.1007/BF00188438. [DOI] [PubMed] [Google Scholar]
  6. Haire R. N., Buell R. D., Litman R. T., Ohta Y., Fu S. M., Honjo T., Matsuda F., de la Morena M., Carro J., Good R. A. Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome. J Exp Med. 1993 Sep 1;178(3):825–834. doi: 10.1084/jem.178.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Haire R. N., Buell R. D., Litman R. T., Ohta Y., Fu S. M., Honjo T., Matsuda F., de la Morena M., Carro J., Good R. A. Diversification, not use, of the immunoglobulin VH gene repertoire is restricted in DiGeorge syndrome. J Exp Med. 1993 Sep 1;178(3):825–834. doi: 10.1084/jem.178.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harding F. A., Cohen N., Litman G. W. Immunoglobulin heavy chain gene organization and complexity in the skate, Raja erinacea. Nucleic Acids Res. 1990 Feb 25;18(4):1015–1020. doi: 10.1093/nar/18.4.1015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hinds K. R., Litman G. W. Major reorganization of immunoglobulin VH segmental elements during vertebrate evolution. Nature. 1986 Apr 10;320(6062):546–549. doi: 10.1038/320546a0. [DOI] [PubMed] [Google Scholar]
  10. Hohman V. S., Schuchman D. B., Schluter S. F., Marchalonis J. J. Genomic clone for sandbar shark lambda light chain: generation of diversity in the absence of gene rearrangement. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):9882–9886. doi: 10.1073/pnas.90.21.9882. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Klein R., Jaenichen R., Zachau H. G. Expressed human immunoglobulin kappa genes and their hypermutation. Eur J Immunol. 1993 Dec;23(12):3248–3262. doi: 10.1002/eji.1830231231. [DOI] [PubMed] [Google Scholar]
  12. Kokubu F., Hinds K., Litman R., Shamblott M. J., Litman G. W. Complete structure and organization of immunoglobulin heavy chain constant region genes in a phylogenetically primitive vertebrate. EMBO J. 1988 Jul;7(7):1979–1988. doi: 10.1002/j.1460-2075.1988.tb03036.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kokubu F., Litman R., Shamblott M. J., Hinds K., Litman G. W. Diverse organization of immunoglobulin VH gene loci in a primitive vertebrate. EMBO J. 1988 Nov;7(11):3413–3422. doi: 10.1002/j.1460-2075.1988.tb03215.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Litman G. W., Berger L., Murphy K., Litman R., Hinds K., Erickson B. W. Immunoglobulin VH gene structure and diversity in Heterodontus, a phylogenetically primitive shark. Proc Natl Acad Sci U S A. 1985 Apr;82(7):2082–2086. doi: 10.1073/pnas.82.7.2082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Litman G. W., Haire R. N., Hinds K. R., Amemiya C. T., Rast J. P., Hulst M. Evolutionary development of the B-cell repertoire. Ann N Y Acad Sci. 1992 May 4;651:360–368. doi: 10.1111/j.1749-6632.1992.tb24636.x. [DOI] [PubMed] [Google Scholar]
  16. Meyerhans A., Vartanian J. P., Wain-Hobson S. DNA recombination during PCR. Nucleic Acids Res. 1990 Apr 11;18(7):1687–1691. doi: 10.1093/nar/18.7.1687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Rast J. P., Anderson M. K., Ota T., Litman R. T., Margittai M., Shamblott M. J., Litman G. W. Immunoglobulin light chain class multiplicity and alternative organizational forms in early vertebrate phylogeny. Immunogenetics. 1994;40(2):83–99. doi: 10.1007/BF00188170. [DOI] [PubMed] [Google Scholar]
  18. Rast J. P., Litman G. W. T-cell receptor gene homologs are present in the most primitive jawed vertebrates. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9248–9252. doi: 10.1073/pnas.91.20.9248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Reynaud C. A., Anquez V., Dahan A., Weill J. C. A single rearrangement event generates most of the chicken immunoglobulin light chain diversity. Cell. 1985 Feb;40(2):283–291. doi: 10.1016/0092-8674(85)90142-4. [DOI] [PubMed] [Google Scholar]
  20. Reynaud C. A., Dahan A., Anquez V., Weill J. C. Somatic hyperconversion diversifies the single Vh gene of the chicken with a high incidence in the D region. Cell. 1989 Oct 6;59(1):171–183. doi: 10.1016/0092-8674(89)90879-9. [DOI] [PubMed] [Google Scholar]
  21. Reynaud C. A., Mackay C. R., Müller R. G., Weill J. C. Somatic generation of diversity in a mammalian primary lymphoid organ: the sheep ileal Peyer's patches. Cell. 1991 Mar 8;64(5):995–1005. doi: 10.1016/0092-8674(91)90323-q. [DOI] [PubMed] [Google Scholar]
  22. Rock E. P., Sibbald P. R., Davis M. M., Chien Y. H. CDR3 length in antigen-specific immune receptors. J Exp Med. 1994 Jan 1;179(1):323–328. doi: 10.1084/jem.179.1.323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saitou N., Nei M. The neighbor-joining method: a new method for reconstructing phylogenetic trees. Mol Biol Evol. 1987 Jul;4(4):406–425. doi: 10.1093/oxfordjournals.molbev.a040454. [DOI] [PubMed] [Google Scholar]
  24. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schild H., Mavaddat N., Litzenberger C., Ehrich E. W., Davis M. M., Bluestone J. A., Matis L., Draper R. K., Chien Y. H. The nature of major histocompatibility complex recognition by gamma delta T cells. Cell. 1994 Jan 14;76(1):29–37. doi: 10.1016/0092-8674(94)90170-8. [DOI] [PubMed] [Google Scholar]
  26. Shamblott M. J., Litman G. W. Complete nucleotide sequence of primitive vertebrate immunoglobulin light chain genes. Proc Natl Acad Sci U S A. 1989 Jun;86(12):4684–4688. doi: 10.1073/pnas.86.12.4684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Shamblott M. J., Litman G. W. Genomic organization and sequences of immunoglobulin light chain genes in a primitive vertebrate suggest coevolution of immunoglobulin gene organization. EMBO J. 1989 Dec 1;8(12):3733–3739. doi: 10.1002/j.1460-2075.1989.tb08549.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tanaka T., Nei M. Positive darwinian selection observed at the variable-region genes of immunoglobulins. Mol Biol Evol. 1989 Sep;6(5):447–459. doi: 10.1093/oxfordjournals.molbev.a040569. [DOI] [PubMed] [Google Scholar]
  29. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  30. Victor K. D., Vu K., Feeney A. J. Limited junctional diversity in kappa light chains. Junctional sequences from CD43+B220+ early B cell progenitors resemble those from peripheral B cells. J Immunol. 1994 Apr 1;152(7):3467–3475. [PubMed] [Google Scholar]
  31. Wu T. T., Kabat E. A. An analysis of the sequences of the variable regions of Bence Jones proteins and myeloma light chains and their implications for antibody complementarity. J Exp Med. 1970 Aug 1;132(2):211–250. doi: 10.1084/jem.132.2.211. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES