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. 1993 Dec 1;178(6):1981–1994. doi: 10.1084/jem.178.6.1981

V(D)J recombination in peritoneal B cells of leaky scid mice

PMCID: PMC2191267  PMID: 8245777

Abstract

Developing lymphocytes in immune-deficient severe combined immunodeficient (scid) mice express a defective recombinase activity and rarely succeed in making an antigen receptor; those cells that do succeed account for the known B and T cell leakiness in this mutant mouse strain. To gain more insight into the nature of the scid defect, we assessed the status of heavy (H) and light (L)k, chain genes in immunoglobulin (Ig)Mk-secreting B cells from the peritoneal cavity of old leaky scid mice, the only lymphoid site where scid B cells have been routinely detected. We found these cells to be unusual in that their nonexpressed H chain alleles were either abnormally rearranged or in germline configuration (wild-type B cells generally show normal rearrangements at both H chain alleles). The VDJH junctions of the expressed alleles showed little or no nontemplated (N) addition, similar to neonatal B cells from wild-type mice. About half of the V(D)J junctions lacking N additions contained nucleotides that could have been encoded by either of the participating coding elements (VDH, DJH, or VJk), indicating that the recombination occurred between short stretches of homology. Unusually long templated (P) additions were seen in both VDJH and VJK junctions, and many recombinations appeared to involve P-based homologies. These findings suggest that: (a) B cell leakiness results from a low frequency of coding joint formation in cells expressing the defective scid recombinase activity; (b) joining of scid coding ends is facilitated when the ends contain short stretches of sequence homology, where in many cases, one of the homologous sequences results from a P addition; and (c) scid peritoneal B cells may arise early in ontogeny.

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Selected References

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  1. Akira S., Okazaki K., Sakano H. Two pairs of recombination signals are sufficient to cause immunoglobulin V-(D)-J joining. Science. 1987 Nov 20;238(4830):1134–1138. doi: 10.1126/science.3120312. [DOI] [PubMed] [Google Scholar]
  2. 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]
  3. Alt F. W., Yancopoulos G. D., Blackwell T. K., Wood C., Thomas E., Boss M., Coffman R., Rosenberg N., Tonegawa S., Baltimore D. Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984 Jun;3(6):1209–1219. doi: 10.1002/j.1460-2075.1984.tb01955.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Asarnow D. M., Cado D., Raulet D. H. Selection is not required to produce invariant T-cell receptor gamma-gene junctional sequences. Nature. 1993 Mar 11;362(6416):158–160. doi: 10.1038/362158a0. [DOI] [PubMed] [Google Scholar]
  5. Benatar T., Tkalec L., Ratcliffe M. J. Stochastic rearrangement of immunoglobulin variable-region genes in chicken B-cell development. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7615–7619. doi: 10.1073/pnas.89.16.7615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blackwell T. K., Malynn B. A., Pollock R. R., Ferrier P., Covey L. R., Fulop G. M., Phillips R. A., Yancopoulos G. D., Alt F. W. Isolation of scid pre-B cells that rearrange kappa light chain genes: formation of normal signal and abnormal coding joins. EMBO J. 1989 Mar;8(3):735–742. doi: 10.1002/j.1460-2075.1989.tb03433.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bosma G. C., Custer R. P., Bosma M. J. A severe combined immunodeficiency mutation in the mouse. Nature. 1983 Feb 10;301(5900):527–530. doi: 10.1038/301527a0. [DOI] [PubMed] [Google Scholar]
  8. Bosma G. C., Fried M., Custer R. P., Carroll A., Gibson D. M., Bosma M. J. Evidence of functional lymphocytes in some (leaky) scid mice. J Exp Med. 1988 Mar 1;167(3):1016–1033. doi: 10.1084/jem.167.3.1016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Carmack C. E., Camper S. A., Mackle J. J., Gerhard W. U., Weigert M. G. Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus. J Immunol. 1991 Sep 15;147(6):2024–2033. [PubMed] [Google Scholar]
  10. Carroll A. M., Bosma M. J. Detection and characterization of functional T cells in mice with severe combined immune deficiency. Eur J Immunol. 1988 Dec;18(12):1965–1971. doi: 10.1002/eji.1830181215. [DOI] [PubMed] [Google Scholar]
  11. Carroll A. M., Hardy R. R., Bosma M. J. Occurrence of mature B (IgM+, B220+) and T (CD3+) lymphocytes in scid mice. J Immunol. 1989 Aug 15;143(4):1087–1093. [PubMed] [Google Scholar]
  12. 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]
  13. Ehlich A., Schaal S., Gu H., Kitamura D., Müller W., Rajewsky K. Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell. 1993 Mar 12;72(5):695–704. doi: 10.1016/0092-8674(93)90398-a. [DOI] [PubMed] [Google Scholar]
  14. Feeney A. J. Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences. J Exp Med. 1990 Nov 1;172(5):1377–1390. doi: 10.1084/jem.172.5.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Feeney A. J. Predominance of VH-D-JH junctions occurring at sites of short sequence homology results in limited junctional diversity in neonatal antibodies. J Immunol. 1992 Jul 1;149(1):222–229. [PubMed] [Google Scholar]
  16. Ferrier P., Covey L. R., Li S. C., Suh H., Malynn B. A., Blackwell T. K., Morrow M. A., Alt F. W. Normal recombination substrate VH to DJH rearrangements in pre-B cell lines from scid mice. J Exp Med. 1990 Jun 1;171(6):1909–1918. doi: 10.1084/jem.171.6.1909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Foster M. H., MacDonald M., Barrett K. J., Madaio M. P. VH gene analysis of spontaneously activated B cells in adult MRL-lpr/lpr mice. J558 bias is not limited to classic lupus autoantibodies. J Immunol. 1991 Sep 1;147(5):1504–1511. [PubMed] [Google Scholar]
  18. Gerstein R. M., Lieber M. R. Extent to which homology can constrain coding exon junctional diversity in V(D)J recombination. Nature. 1993 Jun 17;363(6430):625–627. doi: 10.1038/363625a0. [DOI] [PubMed] [Google Scholar]
  19. Gibson D. M., Bosma G. C., Bosma M. J. Limited clonal diversity of serum immunoglobulin in leaky scid mice. Curr Top Microbiol Immunol. 1989;152:125–136. doi: 10.1007/978-3-642-74974-2_16. [DOI] [PubMed] [Google Scholar]
  20. Gu H., Förster I., Rajewsky K. Sequence homologies, N sequence insertion and JH gene utilization in VHDJH joining: implications for the joining mechanism and the ontogenetic timing of Ly1 B cell and B-CLL progenitor generation. EMBO J. 1990 Jul;9(7):2133–2140. doi: 10.1002/j.1460-2075.1990.tb07382.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gu H., Kitamura D., Rajewsky K. B cell development regulated by gene rearrangement: arrest of maturation by membrane-bound D mu protein and selection of DH element reading frames. Cell. 1991 Apr 5;65(1):47–54. doi: 10.1016/0092-8674(91)90406-o. [DOI] [PubMed] [Google Scholar]
  22. Hardy R. R., Hayakawa K. A developmental switch in B lymphopoiesis. Proc Natl Acad Sci U S A. 1991 Dec 15;88(24):11550–11554. doi: 10.1073/pnas.88.24.11550. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hardy R. R., Hayakawa K. Developmental origins, specificities and immunoglobulin gene biases of murine Ly-1 B cells. Int Rev Immunol. 1992;8(2-3):189–207. doi: 10.3109/08830189209055573. [DOI] [PubMed] [Google Scholar]
  24. Harrington J., Hsieh C. L., Gerton J., Bosma G., Lieber M. R. Analysis of the defect in DNA end joining in the murine scid mutation. Mol Cell Biol. 1992 Oct;12(10):4758–4768. doi: 10.1128/mcb.12.10.4758. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Hayakawa K., Hardy R. R., Herzenberg L. A., Herzenberg L. A. Progenitors for Ly-1 B cells are distinct from progenitors for other B cells. J Exp Med. 1985 Jun 1;161(6):1554–1568. doi: 10.1084/jem.161.6.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hayakawa K., Hardy R. R. Normal, autoimmune, and malignant CD5+ B cells: the Ly-1 B lineage? Annu Rev Immunol. 1988;6:197–218. doi: 10.1146/annurev.iy.06.040188.001213. [DOI] [PubMed] [Google Scholar]
  27. Hayakawa K., Hardy R. R., Stall A. M., Herzenberg L. A., Herzenberg L. A. Immunoglobulin-bearing B cells reconstitute and maintain the murine Ly-1 B cell lineage. Eur J Immunol. 1986 Oct;16(10):1313–1316. doi: 10.1002/eji.1830161021. [DOI] [PubMed] [Google Scholar]
  28. Hendrickson E. A., Schlissel M. S., Weaver D. T. Wild-type V(D)J recombination in scid pre-B cells. Mol Cell Biol. 1990 Oct;10(10):5397–5407. doi: 10.1128/mcb.10.10.5397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Herzenberg L. A., Stall A. M., Lalor P. A., Sidman C., Moore W. A., Parks D. R., Herzenberg L. A. The Ly-1 B cell lineage. Immunol Rev. 1986 Oct;93:81–102. doi: 10.1111/j.1600-065x.1986.tb01503.x. [DOI] [PubMed] [Google Scholar]
  30. Hesse J. E., Lieber M. R., Gellert M., Mizuuchi K. Extrachromosomal DNA substrates in pre-B cells undergo inversion or deletion at immunoglobulin V-(D)-J joining signals. Cell. 1987 Jun 19;49(6):775–783. doi: 10.1016/0092-8674(87)90615-5. [DOI] [PubMed] [Google Scholar]
  31. Holmberg D. High connectivity, natural antibodies preferentially use 7183 and QUPC 52 VH families. Eur J Immunol. 1987 Mar;17(3):399–403. doi: 10.1002/eji.1830170315. [DOI] [PubMed] [Google Scholar]
  32. Ichihara Y., Hayashida H., Miyazawa S., Kurosawa Y. Only DFL16, DSP2, and DQ52 gene families exist in mouse immunoglobulin heavy chain diversity gene loci, of which DFL16 and DSP2 originate from the same primordial DH gene. Eur J Immunol. 1989 Oct;19(10):1849–1854. doi: 10.1002/eji.1830191014. [DOI] [PubMed] [Google Scholar]
  33. Itohara S., Farr A. G., Lafaille J. J., Bonneville M., Takagaki Y., Haas W., Tonegawa S. Homing of a gamma delta thymocyte subset with homogeneous T-cell receptors to mucosal epithelia. Nature. 1990 Feb 22;343(6260):754–757. doi: 10.1038/343754a0. [DOI] [PubMed] [Google Scholar]
  34. Itohara S., Mombaerts P., Lafaille J., Iacomini J., Nelson A., Clarke A. R., Hooper M. L., Farr A., Tonegawa S. T cell receptor delta gene mutant mice: independent generation of alpha beta T cells and programmed rearrangements of gamma delta TCR genes. Cell. 1993 Feb 12;72(3):337–348. doi: 10.1016/0092-8674(93)90112-4. [DOI] [PubMed] [Google Scholar]
  35. Itohara S., Tonegawa S. Selection of gamma delta T cells with canonical T-cell antigen receptors in fetal thymus. Proc Natl Acad Sci U S A. 1990 Oct;87(20):7935–7938. doi: 10.1073/pnas.87.20.7935. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kearney J. F., Solvason N., Stohrer R., Ma J., Van Cleave V., Leheun A., Fulop G., Fried M. Pauciclonal B cell involvement in production of immunoglobulin in scid Ig+ mice. Curr Top Microbiol Immunol. 1989;152:137–147. doi: 10.1007/978-3-642-74974-2_17. [DOI] [PubMed] [Google Scholar]
  37. Kienker L. J., Kuziel W. A., Tucker P. W. T cell receptor gamma and delta gene junctional sequences in SCID mice: excessive P nucleotide insertion. J Exp Med. 1991 Oct 1;174(4):769–773. doi: 10.1084/jem.174.4.769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. 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]
  39. Klinman D. M. Similarities in B cell repertoire development between autoimmune and aging normal mice. J Immunol. 1992 Mar 1;148(5):1353–1358. [PubMed] [Google Scholar]
  40. Kotloff D. B., Bosma M. J., Ruetsch N. R. Scid mouse Pre-B cells with intracellular mu chains: analysis of recombinase activity and IgH gene rearrangements. Int Immunol. 1993 Apr;5(4):383–391. doi: 10.1093/intimm/5.4.383. [DOI] [PubMed] [Google Scholar]
  41. Kubagawa H., Cooper M. D., Carroll A. J., Burrows P. D. Light-chain gene expression before heavy-chain gene rearrangement in pre-B cells transformed by Epstein-Barr virus. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2356–2360. doi: 10.1073/pnas.86.7.2356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Kurosawa Y., Tonegawa S. Organization, structure, and assembly of immunoglobulin heavy chain diversity DNA segments. J Exp Med. 1982 Jan 1;155(1):201–218. doi: 10.1084/jem.155.1.201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Lafaille J. J., DeCloux A., Bonneville M., Takagaki Y., Tonegawa S. Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell. 1989 Dec 1;59(5):859–870. doi: 10.1016/0092-8674(89)90609-0. [DOI] [PubMed] [Google Scholar]
  44. Lewis S. M., Hesse J. E., Mizuuchi K., Gellert M. Novel strand exchanges in V(D)J recombination. Cell. 1988 Dec 23;55(6):1099–1107. doi: 10.1016/0092-8674(88)90254-1. [DOI] [PubMed] [Google Scholar]
  45. 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]
  46. Lieber M. R., Hesse J. E., Lewis S., Bosma G. C., Rosenberg N., Mizuuchi K., Bosma M. J., Gellert M. The defect in murine severe combined immune deficiency: joining of signal sequences but not coding segments in V(D)J recombination. Cell. 1988 Oct 7;55(1):7–16. doi: 10.1016/0092-8674(88)90004-9. [DOI] [PubMed] [Google Scholar]
  47. Marcu K. B., Banerji J., Penncavage N. A., Lang R., Arnheim N. 5' flanking region of immunoglobulin heavy chain constant region genes displays length heterogeneity in germlines of inbred mouse strains. Cell. 1980 Nov;22(1 Pt 1):187–196. doi: 10.1016/0092-8674(80)90167-1. [DOI] [PubMed] [Google Scholar]
  48. McCormack W. T., Tjoelker L. W., Carlson L. M., Petryniak B., Barth C. F., Humphries E. H., Thompson C. B. Chicken IgL gene rearrangement involves deletion of a circular episome and addition of single nonrandom nucleotides to both coding segments. Cell. 1989 Mar 10;56(5):785–791. doi: 10.1016/0092-8674(89)90683-1. [DOI] [PubMed] [Google Scholar]
  49. Meek K. D., Hasemann C. A., Capra J. D. Novel rearrangements at the immunoglobulin D locus. Inversions and fusions add to IgH somatic diversity. J Exp Med. 1989 Jul 1;170(1):39–57. doi: 10.1084/jem.170.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Morzycka-Wroblewska E., Lee F. E., Desiderio S. V. Unusual immunoglobulin gene rearrangement leads to replacement of recombinational signal sequences. Science. 1988 Oct 14;242(4876):261–263. doi: 10.1126/science.3140378. [DOI] [PubMed] [Google Scholar]
  51. Nottenburg C., Weissman I. L. Cmu gene rearrangement of mouse immunoglobulin genes in normal B cells occurs on both the expressed and nonexpressed chromosomes. Proc Natl Acad Sci U S A. 1981 Jan;78(1):484–488. doi: 10.1073/pnas.78.1.484. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Novick K. E., Fasy T. M., Losman M. J., Monestier M. Polyreactive IgM antibodies generated from autoimmune mice and selected for histone-binding activity. Int Immunol. 1992 Oct;4(10):1103–1111. doi: 10.1093/intimm/4.10.1103. [DOI] [PubMed] [Google Scholar]
  53. Pandey A., Tjoelker L. W., Thompson C. B. Restricted immunoglobulin junctional diversity in neonatal B cells results from developmental selection rather than homology-based V(D)J joining. J Exp Med. 1993 Feb 1;177(2):329–337. doi: 10.1084/jem.177.2.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Petrini J. H., Carroll A. M., Bosma M. J. T-cell receptor gene rearrangements in functional T-cell clones from severe combined immune deficient (scid) mice: reversion of the scid phenotype in individual lymphocyte progenitors. Proc Natl Acad Sci U S A. 1990 May;87(9):3450–3453. doi: 10.1073/pnas.87.9.3450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Radic M. Z., Mascelli M. A., Erikson J., Shan H., Weigert M. Ig H and L chain contributions to autoimmune specificities. J Immunol. 1991 Jan 1;146(1):176–182. [PubMed] [Google Scholar]
  56. Reimann J., Rudolphi A., Claesson M. H. CD3+ T-cells in severe combined immunodeficiency (scid) mice. III. Transferred congenic, selfreactive CD4+ T cell clones rescue IgM-producing, scid-derived B cells. Int Immunol. 1991 Jul;3(7):657–663. doi: 10.1093/intimm/3.7.657. [DOI] [PubMed] [Google Scholar]
  57. 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]
  58. Riggs J. E., Stowers R. S., Mosier D. E. Adoptive transfer of neonatal T lymphocytes rescues immunoglobulin production in mice with severe combined immune deficiency. J Exp Med. 1991 Jan 1;173(1):265–268. doi: 10.1084/jem.173.1.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Roth D. B., Menetski J. P., Nakajima P. B., Bosma M. J., Gellert M. V(D)J recombination: broken DNA molecules with covalently sealed (hairpin) coding ends in scid mouse thymocytes. Cell. 1992 Sep 18;70(6):983–991. doi: 10.1016/0092-8674(92)90248-b. [DOI] [PubMed] [Google Scholar]
  60. Roth D. B., Nakajima P. B., Menetski J. P., Bosma M. J., Gellert M. V(D)J recombination in mouse thymocytes: double-strand breaks near T cell receptor delta rearrangement signals. Cell. 1992 Apr 3;69(1):41–53. doi: 10.1016/0092-8674(92)90117-u. [DOI] [PubMed] [Google Scholar]
  61. Roth D. B., Wilson J. H. Nonhomologous recombination in mammalian cells: role for short sequence homologies in the joining reaction. Mol Cell Biol. 1986 Dec;6(12):4295–4304. doi: 10.1128/mcb.6.12.4295. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Schlissel M. S., Baltimore D. Activation of immunoglobulin kappa gene rearrangement correlates with induction of germline kappa gene transcription. Cell. 1989 Sep 8;58(5):1001–1007. doi: 10.1016/0092-8674(89)90951-3. [DOI] [PubMed] [Google Scholar]
  63. Schuler W., Ruetsch N. R., Amsler M., Bosma M. J. Coding joint formation of endogenous T cell receptor genes in lymphoid cells from scid mice: unusual P-nucleotide additions in VJ-coding joints. Eur J Immunol. 1991 Mar;21(3):589–596. doi: 10.1002/eji.1830210309. [DOI] [PubMed] [Google Scholar]
  64. Schuler W., Weiler I. J., Schuler A., Phillips R. A., Rosenberg N., Mak T. W., Kearney J. F., Perry R. P., Bosma M. J. Rearrangement of antigen receptor genes is defective in mice with severe combined immune deficiency. Cell. 1986 Sep 26;46(7):963–972. doi: 10.1016/0092-8674(86)90695-1. [DOI] [PubMed] [Google Scholar]
  65. Shulman M., Wilde C. D., Köhler G. A better cell line for making hybridomas secreting specific antibodies. Nature. 1978 Nov 16;276(5685):269–270. doi: 10.1038/276269a0. [DOI] [PubMed] [Google Scholar]
  66. Sims P. J., Wiedmer T. The response of human platelets to activated components of the complement system. Immunol Today. 1991 Sep;12(9):338–342. doi: 10.1016/0167-5699(91)90012-I. [DOI] [PubMed] [Google Scholar]
  67. Solvason N., Lehuen A., Kearney J. F. An embryonic source of Ly1 but not conventional B cells. Int Immunol. 1991 Jun;3(6):543–550. doi: 10.1093/intimm/3.6.543. [DOI] [PubMed] [Google Scholar]
  68. Stall A. M., Adams S., Herzenberg L. A., Kantor A. B. Characteristics and development of the murine B-1b (Ly-1 B sister) cell population. Ann N Y Acad Sci. 1992 May 4;651:33–43. doi: 10.1111/j.1749-6632.1992.tb24591.x. [DOI] [PubMed] [Google Scholar]
  69. Stall A. M., Fariñas M. C., Tarlinton D. M., Lalor P. A., Herzenberg L. A., Strober S., Herzenberg L. A. Ly-1 B-cell clones similar to human chronic lymphocytic leukemias routinely develop in older normal mice and young autoimmune (New Zealand Black-related) animals. Proc Natl Acad Sci U S A. 1988 Oct;85(19):7312–7316. doi: 10.1073/pnas.85.19.7312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Strohal R., Helmberg A., Kroemer G., Kofler R. Mouse Vk gene classification by nucleic acid sequence similarity. Immunogenetics. 1989;30(6):475–493. doi: 10.1007/BF02421180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Yancopoulos G. D., Alt F. W. Regulation of the assembly and expression of variable-region genes. Annu Rev Immunol. 1986;4:339–368. doi: 10.1146/annurev.iy.04.040186.002011. [DOI] [PubMed] [Google Scholar]

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