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

Publication ,  Journal Article
Shlomchik, M; Mascelli, M; Shan, H; Radic, MZ; Pisetsky, D; Marshak-Rothstein, A; Weigert, M
Published in: J Exp Med
January 1, 1990

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 (19), 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) anti-idiotypes that recognize the majority of anti-DNA are probably not specific for any one family of V regions.

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Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 1, 1990

Volume

171

Issue

1

Start / End Page

265 / 292

Location

United States

Related Subject Headings

  • Species Specificity
  • RNA, Messenger
  • Oligonucleotide Probes
  • Mutation
  • Molecular Sequence Data
  • Mice, Mutant Strains
  • Mice, Inbred Strains
  • Mice
  • Immunology
  • Immunoglobulin kappa-Chains
 

Citation

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Shlomchik, M., Mascelli, M., Shan, H., Radic, M. Z., Pisetsky, D., Marshak-Rothstein, A., & Weigert, M. (1990). Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med, 171(1), 265–292. https://doi.org/10.1084/jem.171.1.265
Shlomchik, M., M. Mascelli, H. Shan, M. Z. Radic, D. Pisetsky, A. Marshak-Rothstein, and M. Weigert. “Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.J Exp Med 171, no. 1 (January 1, 1990): 265–92. https://doi.org/10.1084/jem.171.1.265.
Shlomchik M, Mascelli M, Shan H, Radic MZ, Pisetsky D, Marshak-Rothstein A, et al. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–92.
Shlomchik, M., et al. “Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.J Exp Med, vol. 171, no. 1, Jan. 1990, pp. 265–92. Pubmed, doi:10.1084/jem.171.1.265.
Shlomchik M, Mascelli M, Shan H, Radic MZ, Pisetsky D, Marshak-Rothstein A, Weigert M. Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation. J Exp Med. 1990 Jan 1;171(1):265–292.

Published In

J Exp Med

DOI

ISSN

0022-1007

Publication Date

January 1, 1990

Volume

171

Issue

1

Start / End Page

265 / 292

Location

United States

Related Subject Headings

  • Species Specificity
  • RNA, Messenger
  • Oligonucleotide Probes
  • Mutation
  • Molecular Sequence Data
  • Mice, Mutant Strains
  • Mice, Inbred Strains
  • Mice
  • Immunology
  • Immunoglobulin kappa-Chains