Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation

M. Shlomchik, M. Mascelli, H. Shan, Marko Radic, D. Pisetsky, A. Marshak-Rothstein, M. Weigert

Research output: Contribution to journalArticle

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Abstract

The proximate cause of autoantibodies characteristic of systemic autoimmune diseases has been controversial. One hypothesis is that autoantibodies are the result of polyclonal nonspecific B cell activation. Alternatively, autoantibodies could be the result of antigen-driven B cell activation, as observed in secondary immune responses. We have approached this question by studying monoclonal anti-DNA autoantibodies derived from unmanipulated spleen cells of the autoimmune MRL/lpr mouse strain. This analysis shows that anti-DNAs, like rheumatoid factors, are the result of specific antigen-driven stimulation. In addition, correlation of sequences with fine specificity shows that: (a) somatic mutations can cause specificity for dsDNA and that such mutations are selected for; (b) arginine residues play an important role in determining specificity; and (c) antiidiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.

Original languageEnglish (US)
Pages (from-to)265-297
Number of pages33
JournalJournal of Experimental Medicine
Volume171
Issue number1
DOIs
StatePublished - Feb 2 1990

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Antinuclear Antibodies
Autoantibodies
Mutation
DNA
CD80 Antigens
Inbred MRL lpr Mouse
Rheumatoid Factor
Autoimmune Diseases
Arginine
B-Lymphocytes
Spleen
Antigens

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

Cite this

Shlomchik, M., Mascelli, M., Shan, H., Radic, M., Pisetsky, D., Marshak-Rothstein, A., & Weigert, M. (1990). Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. Journal of Experimental Medicine, 171(1), 265-297. https://doi.org/10.1084/jem.171.1.265

Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. / Shlomchik, M.; Mascelli, M.; Shan, H.; Radic, Marko; Pisetsky, D.; Marshak-Rothstein, A.; Weigert, M.

In: Journal of Experimental Medicine, Vol. 171, No. 1, 02.02.1990, p. 265-297.

Research output: Contribution to journalArticle

Shlomchik, M, Mascelli, M, Shan, H, Radic, M, Pisetsky, D, Marshak-Rothstein, A & Weigert, M 1990, 'Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation', Journal of Experimental Medicine, vol. 171, no. 1, pp. 265-297. https://doi.org/10.1084/jem.171.1.265
Shlomchik, M. ; Mascelli, M. ; Shan, H. ; Radic, Marko ; Pisetsky, D. ; Marshak-Rothstein, A. ; Weigert, M. / Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. In: Journal of Experimental Medicine. 1990 ; Vol. 171, No. 1. pp. 265-297.
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