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Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Sep;86(17):6744–6747. doi: 10.1073/pnas.86.17.6744

Early rearrangements of genes encoding murine immunoglobulin kappa chains, unlike genes encoding heavy chains, use variable gene segments dispersed throughout the locus.

A M Lawler 1, J F Kearney 1, M Kuehl 1, P J Gearhart 1
PMCID: PMC297922  PMID: 2505260

Abstract

Immunoglobulin heavy-chain variable region (TH) gene segments located closest to the joining (JH) gene segments are preferentially rearranged during ontogeny, indicating that chromosomal position influences the frequency of rearrangement. In addition, certain VH gene segments are repeatedly rearranged, suggesting that the DNA sequence or structure surrounding these segments may increase the probability of rearrangement. To determine whether there is similar based rearrangement of kappa variable (V kappa) gene segments, 25 rearrangements were sequenced from murine fetal and neonatal B-cell hybridomas and from subclones of a pre-B cell line that rearranged V kappa genes during in vitro culture. Four gene segments were isolated twice and one gene segment was isolated three times, suggesting that the process that targets individual variable gene segments for repeated rearrangement operates on both the VH and V kappa loci. Based on a current map of the V kappa locus, the rearranged gene segments belong to nine families that are dispersed throughout the locus. Thus, in these cell types, V kappa rearrangements use germ-line gene segments located across the entire locus, whereas the corresponding VH rearrangements use gene segments proximal to the JH gene segments. Heterogeneity of V kappa rearrangements would add diversity to the biased pool of VH rearrangements, producing a broad repertoire of antibodies early in development.

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Selected References

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

  1. Alt F. W., Rosenberg N., Enea V., Siden E., Baltimore D. Multiple immunoglobulin heavy-chain gene transcripts in Abelson murine leukemia virus-transformed lymphoid cell lines. Mol Cell Biol. 1982 Apr;2(4):386–400. doi: 10.1128/mcb.2.4.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barth R. K., Kim B. S., Lan N. C., Hunkapiller T., Sobieck N., Winoto A., Gershenfeld H., Okada C., Hansburg D., Weissman I. L. The murine T-cell receptor uses a limited repertoire of expressed V beta gene segments. Nature. 1985 Aug 8;316(6028):517–523. doi: 10.1038/316517a0. [DOI] [PubMed] [Google Scholar]
  3. Brodeur P. H., Osman G. E., Mackle J. J., Lalor T. M. The organization of the mouse Igh-V locus. Dispersion, interspersion, and the evolution of VH gene family clusters. J Exp Med. 1988 Dec 1;168(6):2261–2278. doi: 10.1084/jem.168.6.2261. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Carroll W. L., Starnes C. O., Levy R., Levy S. Alternative V kappa gene rearrangements in a murine B cell lymphoma. An explantation for idiotypic heterogeneity. J Exp Med. 1988 Nov 1;168(5):1607–1620. doi: 10.1084/jem.168.5.1607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cockerill P. N., Garrard W. T. Chromosomal loop anchorage of the kappa immunoglobulin gene occurs next to the enhancer in a region containing topoisomerase II sites. Cell. 1986 Jan 31;44(2):273–282. doi: 10.1016/0092-8674(86)90761-0. [DOI] [PubMed] [Google Scholar]
  6. D'Hoostelaere L. A., Huppi K., Mock B., Mallett C., Potter M. The Ig kappa L chain allelic groups among the Ig kappa haplotypes and Ig kappa crossover populations suggest a gene order. J Immunol. 1988 Jul 15;141(2):652–661. [PubMed] [Google Scholar]
  7. Dzierzak E. A., Janeway C. A., Jr, Richard N., Bothwell A. Molecular characterization of antibodies bearing Id-460. I. The structure of two highly homologous VH genes used to produce idiotype positive immunoglobulins. J Immunol. 1986 Mar 1;136(5):1864–1870. [PubMed] [Google Scholar]
  8. Even J., Griffiths G. M., Berek C., Milstein C. Light chain germ-line genes and the immune response to 2-phenyloxazolone. EMBO J. 1985 Dec 16;4(13A):3439–3445. doi: 10.1002/j.1460-2075.1985.tb04102.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Feddersen R. M., Van Ness B. G. Double recombination of a single immunoglobulin kappa-chain allele: implications for the mechanism of rearrangement. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4793–4797. doi: 10.1073/pnas.82.14.4793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Heinrich G., Traunecker A., Tonegawa S. Somatic mutation creates diversity in the major group of mouse immunoglobulin kappa light chains. J Exp Med. 1984 Feb 1;159(2):417–435. doi: 10.1084/jem.159.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jeong H. D., Teale J. M. Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression. J Exp Med. 1988 Aug 1;168(2):589–603. doi: 10.1084/jem.168.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kataoka T., Nikaido T., Miyata T., Moriwaki K., Honjo T. The nucleotide sequences of rearranged and germline immunoglobulin VH genes of a mouse myeloma MC101 and evolution of VH genes in mouse. J Biol Chem. 1982 Jan 10;257(1):277–285. [PubMed] [Google Scholar]
  13. Kaushik A., Schulze D. H., Bona C., Kelsoe G. Murine V kappa gene expression does not follow the VH paradigm. J Exp Med. 1989 May 1;169(5):1859–1864. doi: 10.1084/jem.169.5.1859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lawler A. M., Lin P. S., Gearhart P. J. Adult B-cell repertoire is biased toward two heavy-chain variable-region genes that rearrange frequently in fetal pre-B cells. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2454–2458. doi: 10.1073/pnas.84.8.2454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lewis S., Rosenberg N., Alt F., Baltimore D. Continuing kappa-gene rearrangement in a cell line transformed by Abelson murine leukemia virus. Cell. 1982 Oct;30(3):807–816. doi: 10.1016/0092-8674(82)90285-9. [DOI] [PubMed] [Google Scholar]
  16. Nishi M., Kataoka T., Honjo T. Preferential rearrangement of the immunoglobulin kappa chain joining region J kappa 1 and J kappa 2 segments in mouse spleen DNA. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6399–6403. doi: 10.1073/pnas.82.19.6399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Nishioka Y., Leder P. Organization and complete sequence of identical embryonic and plasmacytoma kappa V-region genes. J Biol Chem. 1980 Apr 25;255(8):3691–3694. [PubMed] [Google Scholar]
  18. Perlmutter R. M., Kearney J. F., Chang S. P., Hood L. E. Developmentally controlled expression of immunoglobulin VH genes. Science. 1985 Mar 29;227(4694):1597–1601. doi: 10.1126/science.3975629. [DOI] [PubMed] [Google Scholar]
  19. Potter M., Newell J. B., Rudikoff S., Haber E. Classification of mouse VK groups based on the partial amino acid sequence to the first invariant tryptophan: impact of 14 new sequences from IgG myeloma proteins. Mol Immunol. 1982 Dec;19(12):1619–1630. doi: 10.1016/0161-5890(82)90273-5. [DOI] [PubMed] [Google Scholar]
  20. Reth M. G., Jackson S., Alt F. W. VHDJH formation and DJH replacement during pre-B differentiation: non-random usage of gene segments. EMBO J. 1986 Sep;5(9):2131–2138. doi: 10.1002/j.1460-2075.1986.tb04476.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Sanz I., Capra J. D. V kappa and J kappa gene segments of A/J Ars-A antibodies: somatic recombination generates the essential arginine at the junction of the variable and joining regions. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1085–1089. doi: 10.1073/pnas.84.4.1085. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schroeder H. W., Jr, Hillson J. L., Perlmutter R. M. Early restriction of the human antibody repertoire. Science. 1987 Nov 6;238(4828):791–793. doi: 10.1126/science.3118465. [DOI] [PubMed] [Google Scholar]
  23. Selsing E., Storb U. Somatic mutation of immunoglobulin light-chain variable-region genes. Cell. 1981 Jul;25(1):47–58. doi: 10.1016/0092-8674(81)90230-0. [DOI] [PubMed] [Google Scholar]
  24. Shapiro M. A., Weigert M. How immunoglobulin V kappa genes rearrange. J Immunol. 1987 Dec 1;139(11):3834–3839. [PubMed] [Google Scholar]
  25. Shlomchik M., Nemazee D., van Snick J., Weigert M. Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). II. Comparison of hybridomas derived by lipopolysaccharide stimulation and secondary protein immunization. J Exp Med. 1987 Apr 1;165(4):970–987. doi: 10.1084/jem.165.4.970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Siden E. J., Baltimore D., Clark D., Rosenberg N. E. Immunoglobulin synthesis by lymphoid cells transformed in vitro by Abelson murine leukemia virus. Cell. 1979 Feb;16(2):389–396. doi: 10.1016/0092-8674(79)90014-x. [DOI] [PubMed] [Google Scholar]
  27. Sigal N. H., Gearhart P. J., Press J. L., Klinman N. R. Late acquisition of a germ line antibody specificity. Nature. 1976 Jan 1;259(5538):51–52. doi: 10.1038/259051a0. [DOI] [PubMed] [Google Scholar]
  28. Wood D. L., Coleclough C. Different joining region J elements of the murine kappa immunoglobulin light chain locus are used at markedly different frequencies. Proc Natl Acad Sci U S A. 1984 Aug;81(15):4756–4760. doi: 10.1073/pnas.81.15.4756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Wu G. E., Paige C. J. VH gene family utilization in colonies derived from B and pre-B cells detected by the RNA colony blot assay. EMBO J. 1986 Dec 20;5(13):3475–3481. doi: 10.1002/j.1460-2075.1986.tb04672.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yancopoulos G. D., Desiderio S. V., Paskind M., Kearney J. F., Baltimore D., Alt F. W. Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines. Nature. 1984 Oct 25;311(5988):727–733. doi: 10.1038/311727a0. [DOI] [PubMed] [Google Scholar]
  31. Yancopoulos G. D., Malynn B. A., Alt F. W. Developmentally regulated and strain-specific expression of murine VH gene families. J Exp Med. 1988 Jul 1;168(1):417–435. doi: 10.1084/jem.168.1.417. [DOI] [PMC free article] [PubMed] [Google Scholar]

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