D-PENICILLAMINE-INDUCED AND QUINIDINE-INDUCED ANTINUCLEAR ANTIBODIES IN A.SW (H-2(S)) MICE - SIMILARITIES WITH AUTOANTIBODIES IN SPONTANEOUS AND HEAVY METAL-INDUCED AUTOIMMUNITY

Ten percent of human lupus syndromes occur in patients as a result of treatment with certain medications. H-2(s) mice can produce autoantibo dies following treatment with various drugs or heavy metals and they a re a potential animal model of drug-induced lupus. We have examined ni ne anti-chromatin monoclonal antibodies (mAb) from A.SW mice that had been treated with either D-penicillamine or quinidine, two lupus-induc ing drugs in humans. These mAb are specific either for DNA or histone- DNA complexes corresponding to nucleosomes or subnucleosome particles. Only one mAb reacts with an unknown chromatin antigen. The V region s equences of six of these mAb were studied and are notable by several f eatures. As previously observed in spontaneous autoantibodies to DNA o r histone-DNA complexes, arginine or asparagine residues are found at critical locations throughout the V regions. Many of these residues, p otentially important for binding to DNA or DNA-histone complexes, resu lt either from somatic mutations or atypical V-H-D-J(H) rearrangements . Another significant characteristic is that the V-H genes of several D-penicillamine- or quinidine-induced mAb are most similar to those of anti-nucleolar mAb obtained from mercury-injected A.SW mice. The impl ications of these findings for the pathogenesis of spontaneous or indu ced autoimmunity are discussed.