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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Shlomchik, M; Mascelli, M; Shan, H; Radic, MZ; Pisetsky, D; Marshak-Rothstein, A; Weigert, M

Published Date

  • January 1, 1990

Published In

Volume / Issue

  • 171 / 1

Start / End Page

  • 265 - 292

PubMed ID

  • 2104919

Pubmed Central ID

  • 2104919

International Standard Serial Number (ISSN)

  • 0022-1007

Digital Object Identifier (DOI)

  • 10.1084/jem.171.1.265

Language

  • eng

Conference Location

  • United States