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. 1980 Nov 1;152(5):1302–1310. doi: 10.1084/jem.152.5.1302

Mechanisms of autoantibody production in autoimmune MRL mice

PMCID: PMC2185992  PMID: 7430950

Abstract

The quantitative expression of anti-DNA and anti-Sm antibodies has been investigated in autoimmune MRL-lpr/lpr and MRL-+/+ mice. Anti-Sm antibodies were detected in sera from 21/23 lpr/lpr and 10/16 +/+ mice, with individual animals showing striking variation in the time-course and magnitude of this autoantibody response. The peak antibody levels of the responding animals of each substrain did not differ significantly. For anti-DNA antibody, a different pattern of responsiveness was observed. Individual animals of each substrain produced very similar responses in terms of the magnitude and time- course of serum anti-DNA antibody. The differences in the peak levels of the two substrains were highly significant, with lpr/lpr mice demonstrating a much greater anti-DNA antibody response than +/+ mice. In lpr/lpr mice tested for both autoantibody systems, serum anti-DNA and anti-Sm antibodies showed distinct time-courses. These studies indicate that anti-DNA and anti-Sm antibodies are expressed independently in MRL mice, with the expression of anti-DNA, but not anti-Sm antibody markedly influenced by the presence of the 1pr gene. A fundamental difference in the mechanisms involved in the generation of anti-DNA and anti-Sm antibodies is suggested by the quantitative pattern of the two responses.

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Selected References

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

  1. Akizuki M., Reeves J. P., Steinberg A. D. Expression of autoimmunity by NZB/NZW marrow. Clin Immunol Immunopathol. 1978 Jul;10(3):247–250. doi: 10.1016/0090-1229(78)90177-0. [DOI] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrzejewski C., Jr, Stollar B. D., Lalor T. M., Schwartz R. S. Hybridoma autoantibodies to DNA. J Immunol. 1980 Mar;124(3):1499–1502. [PubMed] [Google Scholar]
  4. Barthold D. R., Kysela S., Steinberg A. D. Decline in suppressor T cell function with age in female NZB mice. J Immunol. 1974 Jan;112(1):9–16. [PubMed] [Google Scholar]
  5. Cerottini J. C., Lambert P. H., Dixon F. J. Comparison of the immune responsiveness of NZB and NZB X NZW F1 hybrid mice with that of other strains of mice. J Exp Med. 1969 Nov 1;130(5):1093–1105. doi: 10.1084/jem.130.5.1093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cohen P. L., Ziff M. Abnormal polyclonal B cell activation in NZB/NZW F1 mice. J Immunol. 1977 Oct;119(4):1534–1537. [PubMed] [Google Scholar]
  7. Creighton W. D., Katz D. H., Dixon F. J. Antigen-specific immunocompetency, B cell function, and regulatory helper and suppressor T cell activities in spontaneously autoimmune mice. J Immunol. 1979 Dec;123(6):2627–2636. [PubMed] [Google Scholar]
  8. DeHeer D. H., Edgington T. S. Evidence for a B lymphocyte defect underlying the anti-X anti-erythrocyte autoantibody response of NZB mice. J Immunol. 1977 May;118(5):1858–1863. [PubMed] [Google Scholar]
  9. Eisenberg R. A., Tan E. M., Dixon F. J. Presence of anti-Sm reactivity in autoimmune mouse strains. J Exp Med. 1978 Feb 1;147(2):582–587. doi: 10.1084/jem.147.2.582. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Evans M. M., Williamson W. G., Irvine W. J. The appearance of immunological competence at an early age in New Zealand black mice. Clin Exp Immunol. 1968 Jun;3(5):375–383. [PMC free article] [PubMed] [Google Scholar]
  11. Gerber N. L., Hardin J. A., Chused T. M., Steinberg A. D. Loss with age in NZB-W mice of thymic suppressor cells in the graft-vs-host reaction. J Immunol. 1974 Nov;113(5):1618–1625. [PubMed] [Google Scholar]
  12. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  13. Izui S., Kobayakawa T., Zryd M. J., Louis J., Lambert P. H. Mechanism for induction of anti-DNA antibodies by bacterial lipopolysaccharides in mice; II. Correlation between anti-DNA induction and polyclonal antibody formation by various polyclonal B lymphocyte activators. J Immunol. 1977 Dec;119(6):2157–2162. [PubMed] [Google Scholar]
  14. 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]
  15. Manny N., Datta S. K., Schwartz R. S. Synthesis of IgM by cells of NZB and SWR mice and their crosses. J Immunol. 1979 Apr;122(4):1220–1227. [PubMed] [Google Scholar]
  16. Nakamura R. M., Peebles C. L., Tan E. M. Microhemagglutination test for detection of antibodies to nuclear Sm and ribonucleoprotein antigens in systemic lupus erythematosus and related diseases. Am J Clin Pathol. 1978 Nov;70(5):800–807. doi: 10.1093/ajcp/70.5.800. [DOI] [PubMed] [Google Scholar]
  17. Pincus T., Schur P. H., Rose J. A., Decker J. L., Talal N. Measurement of serum DNA-binding activity in systemic lupus erythematosus. N Engl J Med. 1969 Sep 25;281(13):701–705. doi: 10.1056/NEJM196909252811304. [DOI] [PubMed] [Google Scholar]
  18. Schur P. H., Sandson J. Immunologic factors and clinical activity in systemic lupus erythematosus. N Engl J Med. 1968 Mar 7;278(10):533–538. doi: 10.1056/NEJM196803072781004. [DOI] [PubMed] [Google Scholar]
  19. Sharp G. C., Irvin W. S., May C. M., Holman H. R., McDuffie F. C., Hess E. V., Schmid F. R. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases. N Engl J Med. 1976 Nov 18;295(21):1149–1154. doi: 10.1056/NEJM197611182952101. [DOI] [PubMed] [Google Scholar]
  20. Staples P. J., Talal N. Relative inability to induce tolerance in adult NZB and NZB-NZW F1 mice. J Exp Med. 1969 Jan 1;129(1):123–139. doi: 10.1084/jem.129.1.123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tan E. M., Kunkel H. G. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966 Mar;96(3):464–471. [PubMed] [Google Scholar]
  22. Tan E. M., Schur P. H., Carr R. I., Kunkel H. G. Deoxybonucleic acid (DNA) and antibodies to DNA in the serum of patients with systemic lupus erythematosus. J Clin Invest. 1966 Nov;45(11):1732–1740. doi: 10.1172/JCI105479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Theofilopoulos A. N., Eisenberg R. A., Bourdon M., Crowell J. S., Jr, Dixon F. J. Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med. 1979 Feb 1;149(2):516–534. doi: 10.1084/jem.149.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Weir D. M., McBride W., Naysmith J. D. Immune response to a soluble protein antigen in NZB mice. Nature. 1968 Sep 21;219(5160):1276–1277. doi: 10.1038/2191276a0. [DOI] [PubMed] [Google Scholar]

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