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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Oct;86(1):106–111. doi: 10.1111/j.1365-2249.1991.tb05781.x

Qualitative difference of anti-DNA antibody-producing cell precursors in the pre-immune B cell repertoire between normal and lupus-prone mice.

K Iwai 1, T Tsubata 1, Y Katsura 1, S Kumagai 1, H Imura 1
PMCID: PMC1554172  PMID: 1914223

Abstract

The precursor frequency for anti-DNA antibody-producing cells in the pre-immune B cell repertoire was investigated in young female BALB/c and NZW mice, and in young and aged female NZB x NZWF1 (B/WF1) mice. Spleen cells from these mice were diluted serially and stimulated polyclonally in vitro with lipopolysaccharide (LPS) and IL-4 to induce both IgM and IgG1 production. The results demonstrated that there existed virtually no difference in precursor frequency for IgM anti-DNA antibody-producing cells between normal and lupus mice, confirming previous observations made by other investigators. In contrast, the number of precursors for IgG1 anti-DNA antibody-producing cells was much higher in young and old B/WF1 mice than in normal mice. These results suggest that the high frequency of precursors for IgG1 anti-DNA antibody-producing cells in the pre-immune B cell repertoire of B/WF1 mice is a crucial factor for the pathogenesis of systemic lupus erythematosus.

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Selected References

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

  1. Andersson J., Coutinho A., Melchers F. Frequencies of mitogen-reactive B cells in the mouse. II. Frequencies of B cells producing antibodies which lyse sheep or horse erythrocytes, and trinitrophenylated or nitroiodophenylated sheep erythrocytes. J Exp Med. 1977 Jun 1;145(6):1520–1530. doi: 10.1084/jem.145.6.1520. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Behar S. M., Scharff M. D. Somatic diversification of the S107 (T15) VH11 germ-line gene that encodes the heavy-chain variable region of antibodies to double-stranded DNA in (NZB x NZW)F1 mice. Proc Natl Acad Sci U S A. 1988 Jun;85(11):3970–3974. doi: 10.1073/pnas.85.11.3970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bergstedt-Lindqvist S., Moon H. B., Persson U., Möller G., Heusser C., Severinson E. Interleukin 4 instructs uncommitted B lymphocytes to switch to IgG1 and IgE. Eur J Immunol. 1988 Jul;18(7):1073–1077. doi: 10.1002/eji.1830180716. [DOI] [PubMed] [Google Scholar]
  4. Conger J. D., Pike B. L., Nossal G. J. Clonal analysis of the anti-DNA repertoire of murine B lymphocytes. Proc Natl Acad Sci U S A. 1987 May;84(9):2931–2935. doi: 10.1073/pnas.84.9.2931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cowdery J. S., Jacobi S. M., Pitts A. K., Tyler T. L. Defective B cell clonal regulation and autoantibody production in New Zealand black mice. J Immunol. 1987 Feb 1;138(3):760–764. [PubMed] [Google Scholar]
  6. Dersimonian H., Schwartz R. S., Barrett K. J., Stollar B. D. Relationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies. J Immunol. 1987 Oct 1;139(7):2496–2501. [PubMed] [Google Scholar]
  7. Eaton R. B., Schnneider G., Schur P. H. Enzyme immunoassay for antibodies to native DNA. Specificity and quality of antibodies. Arthritis Rheum. 1983 Jan;26(1):52–62. doi: 10.1002/art.1780260109. [DOI] [PubMed] [Google Scholar]
  8. Eilat D., Hochberg M., Tron F., Jacob L., Bach J. F. The VH gene sequences of anti-DNA antibodies in two different strains of lupus-prone mice are highly related. Eur J Immunol. 1989 Jul;19(7):1241–1246. doi: 10.1002/eji.1830190714. [DOI] [PubMed] [Google Scholar]
  9. Eilat D., Webster D. M., Rees A. R. V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice. J Immunol. 1988 Sep 1;141(5):1745–1753. [PubMed] [Google Scholar]
  10. Holmberg D., Freitas A. A., Portnoï D., Jacquemart F., Avrameas S., Coutinho A. Antibody repertoires of normal BALB/c mice: B lymphocyte populations defined by state of activation. Immunol Rev. 1986 Oct;93:147–169. doi: 10.1111/j.1600-065x.1986.tb01506.x. [DOI] [PubMed] [Google Scholar]
  11. Isakson P. C., Puré E., Vitetta E. S., Krammer P. H. T cell-derived B cell differentiation factor(s). Effect on the isotype switch of murine B cells. J Exp Med. 1982 Mar 1;155(3):734–748. doi: 10.1084/jem.155.3.734. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Izui S., McConahey P. J., Dixon F. J. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed] [Google Scholar]
  13. Izui S., Zaldivar N. M., Scher I., Lambert P. H. Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice. I. Anti-DNA induction by LPS without significant release of DNA in circulating blood. J Immunol. 1977 Dec;119(6):2151–2156. [PubMed] [Google Scholar]
  14. Jyonouchi H., Kincade P. W., Good R. A., Gershwin M. E. B lymphocyte lineage cells in newborn and very young NZB mice: evidence for regulatory disorders affecting B cell formation. J Immunol. 1983 Nov;131(5):2219–2225. [PubMed] [Google Scholar]
  15. Karasuyama H., Melchers F. Establishment of mouse cell lines which constitutively secrete large quantities of interleukin 2, 3, 4 or 5, using modified cDNA expression vectors. Eur J Immunol. 1988 Jan;18(1):97–104. doi: 10.1002/eji.1830180115. [DOI] [PubMed] [Google Scholar]
  16. Klinman D. M., Eisenberg R. A., Steinberg A. D. Development of the autoimmune B cell repertoire in MRL-lpr/lpr mice. J Immunol. 1990 Jan 15;144(2):506–511. [PubMed] [Google Scholar]
  17. Klinman N. R. The mechanism of antigenic stimulation of primary and secondary clonal precursor cells. J Exp Med. 1972 Aug 1;136(2):241–260. doi: 10.1084/jem.136.2.241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kohno A., Yoshida H., Sekita K., Maruyama N., Ozaki S., Hirose S., Shirai T. Genetic regulation of the class conversion of dsDNA-specific antibodies in (NZB X NZW)F1 hybrid. Immunogenetics. 1983;18(5):513–524. doi: 10.1007/BF00364392. [DOI] [PubMed] [Google Scholar]
  19. McHeyzer-Williams M. G., Nossal G. J. Clonal analysis of autoantibody-producing cell precursors in the preimmune B cell repertoire. J Immunol. 1988 Dec 15;141(12):4118–4123. [PubMed] [Google Scholar]
  20. Nishikawa S., Takemori T., Rajewsky K. The expression of a set of antibody variable regions in lipopolysaccharide-reactive B cells at various stages of ontogeny and its control by anti-idiotypic antibody. Eur J Immunol. 1983 Apr;13(4):318–325. doi: 10.1002/eji.1830130409. [DOI] [PubMed] [Google Scholar]
  21. Noma Y., Sideras P., Naito T., Bergstedt-Lindquist S., Azuma C., Severinson E., Tanabe T., Kinashi T., Matsuda F., Yaoita Y. Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature. 1986 Feb 20;319(6055):640–646. doi: 10.1038/319640a0. [DOI] [PubMed] [Google Scholar]
  22. Papoian R., Pillarisetty R., Talal N. Immunological regulation of spontaneous antibodies to DNA and RNA. II. Sequential switch from IgM to IgG in NZB/NZW F1 mice. Immunology. 1977 Jan;32(1):75–79. [PMC free article] [PubMed] [Google Scholar]
  23. Pisetsky D. S., Caster S. A. The B-cell repertoire for autoantibodies: frequency of precursor cells for anti-DNA antibodies. Cell Immunol. 1982 Sep 15;72(2):294–305. doi: 10.1016/0008-8749(82)90477-4. [DOI] [PubMed] [Google Scholar]
  24. Sawada S., Pillarisetty R. J., Michalski J. P., Palmer D. W., Talal N. Lymphocytes binding polyriboadenylic acid and synthesizing antibodies to nucleic acids in autoimmune and normal mice. J Immunol. 1977 Jul;119(1):355–360. [PubMed] [Google Scholar]
  25. Shlomchik M. J., Aucoin A. H., Pisetsky D. S., Weigert M. G. Structure and function of anti-DNA autoantibodies derived from a single autoimmune mouse. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9150–9154. doi: 10.1073/pnas.84.24.9150. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Slack J. H., Hang L., Barkley J., Fulton R. J., D'Hoostelaere L., Robinson A., Dixon F. J. Isotypes of spontaneous and mitogen-induced autoantibodies in SLE-prone mice. J Immunol. 1984 Mar;132(3):1271–1275. [PubMed] [Google Scholar]
  27. Steward M. W., Hay F. C. Changes in immunoglobulin class and subclass of anti-DNA antibodies with increasing age in N/ZBW F1 hybrid mice. Clin Exp Immunol. 1976 Nov;26(2):363–370. [PMC free article] [PubMed] [Google Scholar]
  28. Theofilopoulos A. N., Shawler D. L., Eisenberg R. A., Dixon F. J. Splenic immunoglobulin-secreting cells and their regulation in autoimmune mice. J Exp Med. 1980 Feb 1;151(2):446–466. doi: 10.1084/jem.151.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tsubata T., Nishikawa S., Katsura Y., Kumagai S., Imura H. B cell repertoire for anti-DNA antibody in normal and lupus mice: differential expression of precursor cells for high and low affinity anti-DNA antibodies. Clin Exp Immunol. 1988 Jan;71(1):50–55. [PMC free article] [PubMed] [Google Scholar]
  30. Winfield J. B., Faiferman I., Koffler D. Avidity of anti-DNA antibodies in serum and IgG glomerular eluates from patients with systemic lupus erythematosus. Association of high avidity antinative DNA antibody with glomerulonephritis. J Clin Invest. 1977 Jan;59(1):90–96. doi: 10.1172/JCI108626. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yoshida H., Yoshida M., Izui S., Lambert P. H. Distinct clonotypes of anti-DNA antibodies in mice with lupus nephritis. J Clin Invest. 1985 Aug;76(2):685–694. doi: 10.1172/JCI112022. [DOI] [PMC free article] [PubMed] [Google Scholar]

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