INDUCTION OF AN ANTI-FAB, ANTI-DNA AND ANTI-RNA POLYMERASE I AUTOANTIBODY RESPONSE NETWORK IN RABBITS IMMUNIZED WITH SLE ANTI-DNA ANTIBODY

Systemic lupus erythematosus (SLE)-like anti-IgG Fab autoantibodies (a utoAb) were induced in rabbits by immunization with either human, mous e or rabbit anti-DNA Ab. In direct-binding radioimmunoassay (RIA), aff inity-purified anti-normal rabbit (NR) Fab autoAb cross-reacted with n ormal mouse (NM) Fab, ssDNA (but not dsDNA), poly(dA,dT), and RNA poly merase I (RPI). Affinity-purified anti-NM IgG Ab isolated from the sam e antisera cross-reacted with NR Fab, ssDNA and RPI. In inhibition RIA , soluble NR Fab inhibited anti-NR Fab binding to NR Fab and ssDNA, bu t enhanced binding to RPI. In contrast, ssDNA or RPI inhibitors had no effect upon autoAb binding to NR Fab. Anti-DNA, anti-RPI and anti-RPI 190 kD subunit autoAb, induced by immunization with lupus mouse anti- DNA Ab, also reacted with NM Fab, but were idiotypically specific for lupus mouse anti-DNA Fab. Further, rabbit anti-DNA and anti-RPI IgG au toAb, induced by immunization with rabbit anti-DNA IgG, were each idio typically specific for homologous and autologous rabbit anti-ssDNA Fab . Together, these data provide evidence that anti-DNA, anti-RPI and an ti-Fab autoAb are linked in a complex, multiple-specific and perhaps r egulatory, immune response idiotype network in SLE.