Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation.
Journal Article (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
- PMC2187662
International Standard Serial Number (ISSN)
- 0022-1007
Digital Object Identifier (DOI)
- 10.1084/jem.171.1.265
Language
- eng
Conference Location
- United States