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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
Journal of Experimental Medicine. 1990 ;171(1) :265-297
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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.
00221007 (ISSN) Cited By: 229; Export Date: 30 May 2006; Source: Scopus CODEN: JEMEA Language of Original Document: English Correspondence Address: Weigert, M.; Institute for Cancer Research; Fox Chase Cancer Center; 7701 Burholme Avenue Philadelphia, PA 19111, United States Molecular Sequence Numbers: GENBANK: UNKNOWN; Chemicals/CAS: Antibodies, Monoclonal; Autoantibodies; DNA, 9007-49-2; DNA, Single-Stranded; Immunoglobulin Joining Region; Immunoglobulin Variable Region; Immunoglobulins, Heavy-Chain; Immunoglobulins, kappa-Chain; Oligonucleotide Probes; RNA, Messenger