INDUCTION OF ANTI-POLYCATION ANTIBODIES IN H-2(S) MICE BY IMMUNIZATION WITH NUCLEAR ANTIGENS

Following administration of certain chemicals (heavy metals or lupus-i nducing drugs), H-2(s) mice produce autoantibodies reacting with vario us nuclear antigens such as fibrillarin in the nucleolus and histones in chromatin. In the present study, we have immunized A.SW (H-2(s)) mi ce and their congenic counterparts A.BY (H-2(b)) mice with bovine thym us nuclei in Freund's adjuvant. As was previously observed with lupus- prone mice, such active immunization did not elicit antinuclear antibo dies in any of the experimental groups. Surprisingly, the A.SW immuniz ed with nuclei in adjuvant developed high titers of IgG antibodies tha t reacted exclusively with synthetic polycations. We obtained several monoclonal IgG antibodies from these mice and verified that these poly cation-reactive antibodies were not directed against a specific nuclea r antigen. The genetic analysis of the monoclonal antibodies further c onfirmed their clonal diversity. The mechanisms leading to the appeara nce of antibodies reactive with highly basic molecules in A.SW mice ma y be related to their predisposition to produce autoantibodies to cati onic nuclear antigens (fibrillarin, histones) during chemically-induce d autoimmunity. (C) 1997 Elsevier Science Ltd.