INDUCTION OF LUPUS-ASSOCIATED AUTOANTIBODIES BY IMMUNIZATION WITH NATIVE AND RECOMBINANT IG POLYPEPTIDES EXPRESSING A CROSS-REACTIVE IDIOTYPE 4B4

A human mAb designated 4B4 with anti-Sm activity was derived from a pa tient with systemic lupus erythematosus. This antibody expressed a lup us-associated cross-reactive Id, partially related to the monoclonal m urine anti-Sm (Y2) from MRL/lpr mice. Studies were performed to invest igate the ability of 4B4 to induce lupus in nonautoimmune-prone mice. BALB/c mice immunized with 4B4 produced antibodies to dsDNA, ssDNA, Sm ribonucleoprotein, and mouse Fc fragment. There was no antibody activ ity against SSA/Ro, SSB/La, and hen egg lysozyme. Ag inhibition studie s show that the autoantibodies were not polyreactive. Mice were also i mmunized with r4B4 polypeptides representing the H/L heterodimer, H ch ain and L chain. Autoantibodies were induced in mice immunized against the H/L and H polypeptides. No autoantibodies were induced in mice im munized with recombinant L chain. Furthermore, from 20 to 68% of antib ody activity to Sm or dsDNA could be inhibited with anti-Id antiserum (either anti-4B4 or Y2). The autoantibody was initially IgM and then u nderwent an isotype switch to IgG. These results show that lupus-assoc iated autoantibodies can be induced by immunization with 4B4 and that the 4B4 V(H) region is important in this induction process. The findin g of murine IgG autoantibody expressing a cross-reactive Id similar to the immunizing 4B4 suggests a role for anti-idiotypic Th cells in thi s autoimmune response.