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. 1990 Feb;10(2):569–576. doi: 10.1128/mcb.10.2.569

Corrective recombination of mouse immunoglobulin kappa alleles in Abelson murine leukemia virus-transformed pre-B cells.

R M Feddersen 1, B G Van Ness 1
PMCID: PMC360841  PMID: 2153918

Abstract

Previous characterization of mouse immunoglobulin kappa gene rearrangement products cloned from murine plasmacytomas has indicated that two recombination events can take place on a single kappa allele (R. M. Feddersen and B. G. Van Ness, Proc. Natl. Acad. Sci. USA 82:4792-4797, 1985; M. A. Shapiro and M. Weigert, J. Immunol. 139:3834-3839, 1987). To determine whether multiple recombinations on a single kappa allele can contribute to the formation of productive V-J genes through corrective recombinations, we have examined several Abelson murine leukemia virus-transformed pre-B-cell clones which rearrange the kappa locus during cell culture. Clonal cell lines which had rearranged one kappa allele nonproductively while maintaining the other allele in the germ line configuration were grown, and secondary subclones, which subsequently expressed kappa protein, were isolated and examined for further kappa rearrangement. A full spectrum of rearrangement patterns was observed in this sequential cloning, including productive and nonproductive recombinations of the germ line allele and secondary recombinations of the nonproductive allele. The results show that corrective V-J recombinations, with displacement of the nonproductive kappa gene, occur with a significant frequency (6 of 17 kappa-producing subclones). Both deletion and maintenance of the primary (nonfunctional) V-J join, as a reciprocal product, were observed.

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Selected References

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  1. Alt F. W., Baltimore D. Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4118–4122. doi: 10.1073/pnas.79.13.4118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alt F. W., Blackwell T. K., Yancopoulos G. D. Development of the primary antibody repertoire. Science. 1987 Nov 20;238(4830):1079–1087. doi: 10.1126/science.3317825. [DOI] [PubMed] [Google Scholar]
  3. Altenburger W., Steinmetz M., Zachau H. G. Functional and non-functional joining in immunoglobulin light chain genes of a mouse myeloma. Nature. 1980 Oct 16;287(5783):603–607. doi: 10.1038/287603a0. [DOI] [PubMed] [Google Scholar]
  4. Baer R., Boehm T., Yssel H., Spits H., Rabbitts T. H. Complex rearrangements within the human J delta-C delta/J alpha-C alpha locus and aberrant recombination between J alpha segments. EMBO J. 1988 Jun;7(6):1661–1668. doi: 10.1002/j.1460-2075.1988.tb02993.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baumann B., Potash M. J., Köhler G. Consequences of frameshift mutations at the immunoglobulin heavy chain locus of the mouse. EMBO J. 1985 Feb;4(2):351–359. doi: 10.1002/j.1460-2075.1985.tb03636.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bernard O., Gough N. M., Adams J. M. Plasmacytomas with more than one immunoglobulin kappa mRNA: implications for allelic exclusion. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5812–5816. doi: 10.1073/pnas.78.9.5812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blackwell T. K., Moore M. W., Yancopoulos G. D., Suh H., Lutzker S., Selsing E., Alt F. W. Recombination between immunoglobulin variable region gene segments is enhanced by transcription. Nature. 1986 Dec 11;324(6097):585–589. doi: 10.1038/324585a0. [DOI] [PubMed] [Google Scholar]
  8. Choi E., Kuehl M., Wall R. RNA splicing generates a variant light chain from an aberrantly rearranged kappa gene. Nature. 1980 Aug 21;286(5775):776–779. doi: 10.1038/286776a0. [DOI] [PubMed] [Google Scholar]
  9. Coleclough C., Perry R. P., Karjalainen K., Weigert M. Aberrant rearrangements contribute significantly to the allelic exclusion of immunoglobulin gene expression. Nature. 1981 Apr 2;290(5805):372–378. doi: 10.1038/290372a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Höchtl J., Müller C. R., Zachau H. G. Recombined flanks of the variable and joining segments of immunoglobulin genes. Proc Natl Acad Sci U S A. 1982 Mar;79(5):1383–1387. doi: 10.1073/pnas.79.5.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kelley D. E., Wiedemann L. M., Pittet A. C., Strauss S., Nelson K. J., Davis J., Van Ness B., Perry R. P. Nonproductive kappa immunoglobulin genes: recombinational abnormalities and other lesions affecting transcription, RNA processing, turnover, and translation. Mol Cell Biol. 1985 Jul;5(7):1660–1675. doi: 10.1128/mcb.5.7.1660. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kleinfield R. W., Weigert M. G. Analysis of VH gene replacement events in a B cell lymphoma. J Immunol. 1989 Jun 15;142(12):4475–4482. [PubMed] [Google Scholar]
  14. Kleinfield R., Hardy R. R., Tarlinton D., Dangl J., Herzenberg L. A., Weigert M. Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma. 1986 Aug 28-Sep 3Nature. 322(6082):843–846. doi: 10.1038/322843a0. [DOI] [PubMed] [Google Scholar]
  15. Kwan S. P., Max E. E., Seidman J. G., Leder P., Scharff M. D. Two kappa immunoglobulin genes are expressed in the myeloma S107. Cell. 1981 Oct;26(1 Pt 1):57–66. doi: 10.1016/0092-8674(81)90033-7. [DOI] [PubMed] [Google Scholar]
  16. Lawler A. M., Kearney J. F., Kuehl M., Gearhart P. J. Early rearrangements of genes encoding murine immunoglobulin kappa chains, unlike genes encoding heavy chains, use variable gene segments dispersed throughout the locus. Proc Natl Acad Sci U S A. 1989 Sep;86(17):6744–6747. doi: 10.1073/pnas.86.17.6744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lewis S., Gifford A., Baltimore D. DNA elements are asymmetrically joined during the site-specific recombination of kappa immunoglobulin genes. Science. 1985 May 10;228(4700):677–685. doi: 10.1126/science.3158075. [DOI] [PubMed] [Google Scholar]
  18. Lewis S., Gifford A., Baltimore D. Joining of V kappa to J kappa gene segments in a retroviral vector introduced into lymphoid cells. 1984 Mar 29-Apr 4Nature. 308(5958):425–428. doi: 10.1038/308425a0. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Marolleau J. P., Fondell J. D., Malissen M., Trucy J., Barbier E., Marcu K. B., Cazenave P. A., Primi D. The joining of germ-line V alpha to J alpha genes replaces the preexisting V alpha-J alpha complexes in a T cell receptor alpha, beta positive T cell line. Cell. 1988 Oct 21;55(2):291–300. doi: 10.1016/0092-8674(88)90052-9. [DOI] [PubMed] [Google Scholar]
  21. Mathur A., Lynch R. G., Köhler G. The contribution of constant region domains to the binding of murine IgM to Fc mu receptors on T cells. J Immunol. 1988 Jan 1;140(1):143–147. [PubMed] [Google Scholar]
  22. Max E. E., Seidman J. G., Miller H., Leder P. Variation in the crossover point of kappa immunoglobulin gene V-J recombination: evidence from a cryptic gene. Cell. 1980 Oct;21(3):793–799. doi: 10.1016/0092-8674(80)90442-0. [DOI] [PubMed] [Google Scholar]
  23. Okazaki K., Davis D. D., Sakano H. T cell receptor beta gene sequences in the circular DNA of thymocyte nuclei: direct evidence for intramolecular DNA deletion in V-D-J joining. Cell. 1987 May 22;49(4):477–485. doi: 10.1016/0092-8674(87)90450-8. [DOI] [PubMed] [Google Scholar]
  24. Okazaki K., Sakano H. Thymocyte circular DNA excised from T cell receptor alpha-delta gene complex. EMBO J. 1988 Jun;7(6):1669–1674. doi: 10.1002/j.1460-2075.1988.tb02994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perry R. P., Coleclough C., Weigert M. Reorganization and expression of immunoglobulin genes: status of allelic elements. Cold Spring Harb Symp Quant Biol. 1981;45(Pt 2):925–933. doi: 10.1101/sqb.1981.045.01.109. [DOI] [PubMed] [Google Scholar]
  26. Perry R. P., Kelley D. E., Coleclough C., Seidman J. G., Leder P., Tonegawa S., Matthyssens G., Weigert M. Transcription of mouse kappa chain genes: implications for allelic exclusion. Proc Natl Acad Sci U S A. 1980 Apr;77(4):1937–1941. doi: 10.1073/pnas.77.4.1937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Perry R. P., Kelley D. E. Immunoglobulin messenger RNAs in murine cell lines that have characteristics of immature B lymphocytes. Cell. 1979 Dec;18(4):1333–1339. doi: 10.1016/0092-8674(79)90243-5. [DOI] [PubMed] [Google Scholar]
  28. Reth M. G., Ammirati P., Jackson S., Alt F. W. Regulated progression of a cultured pre-B-cell line to the B-cell stage. 1985 Sep 26-Oct 2Nature. 317(6035):353–355. doi: 10.1038/317353a0. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. Reth M., Gehrmann P., Petrac E., Wiese P. A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production. 1986 Aug 28-Sep 3Nature. 322(6082):840–842. doi: 10.1038/322840a0. [DOI] [PubMed] [Google Scholar]
  31. Seidman J. G., Leder P. A mutant immunoglobulin light chain is formed by aberrant DNA- and RNA-splicing events. Nature. 1980 Aug 21;286(5775):779–783. doi: 10.1038/286779a0. [DOI] [PubMed] [Google Scholar]
  32. Selsing E., Voss J., Storb U. Immunoglobulin gene 'remnant' DNA--implications for antibody gene recombination. Nucleic Acids Res. 1984 May 25;12(10):4229–4246. doi: 10.1093/nar/12.10.4229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Shapiro M. A., Weigert M. How immunoglobulin V kappa genes rearrange. J Immunol. 1987 Dec 1;139(11):3834–3839. [PubMed] [Google Scholar]
  34. Steinmetz M., Altenburger W., Zachau H. G. A rearranged DNA sequence possibly related to the translocation of immunoglobulin gene segments. Nucleic Acids Res. 1980 Apr 25;8(8):1709–1720. doi: 10.1093/nar/8.8.1709. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Steinmetz M., Zachau H. G. Two rearranged immunoglobulin kappa light chain genes in one mouse myeloma. Nucleic Acids Res. 1980 Apr 25;8(8):1693–1707. doi: 10.1093/nar/8.8.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Tonegawa S. Somatic generation of antibody diversity. Nature. 1983 Apr 14;302(5909):575–581. doi: 10.1038/302575a0. [DOI] [PubMed] [Google Scholar]
  37. Van Ness B. G., Coleclough C., Perry R. P., Weigert M. DNA between variable and joining gene segments of immunoglobulin kappa light chain is frequently retained in cells that rearrange the kappa locus. Proc Natl Acad Sci U S A. 1982 Jan;79(2):262–266. doi: 10.1073/pnas.79.2.262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. VanNess B. G., Shapiro M., Kelley D. E., Perry R. P., Weigert M., D'Eustachio P., Ruddle F. Aberrant rearrangement of the kappa light-chain locus involving the heavy-chain locus and chromosome 15 in a mouse plasmacytoma. Nature. 1983 Feb 3;301(5899):425–427. doi: 10.1038/301425a0. [DOI] [PubMed] [Google Scholar]
  39. Walfield A., Selsing E., Arp B., Storb U. Misalignment of V and J gene segments resulting in a nonfunctional immunoglobulin gene. Nucleic Acids Res. 1981 Mar 11;9(5):1101–1109. doi: 10.1093/nar/9.5.1101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Wysocki L. J., Sato V. L. "Panning" for lymphocytes: a method for cell selection. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2844–2848. doi: 10.1073/pnas.75.6.2844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Yancopoulos G. D., Alt F. W. Developmentally controlled and tissue-specific expression of unrearranged VH gene segments. Cell. 1985 Feb;40(2):271–281. doi: 10.1016/0092-8674(85)90141-2. [DOI] [PubMed] [Google Scholar]

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