Induction of an anti-Fab, anti-DNA and anti-RNA polymerase I autoantibody response network in rabbits immunized with SLE anti-DNA antibody

Abstract

Systemic lupus erythematosus (SLE)-like anti-IgG Fab autoantibodies (autoAb) were induced in rabbits by immunization with either human, mouse or rabbit anti-DNA Ab. In direct-binding radioimmunoassay (RIA), affinity-purified anti-normal rabbit (NR) Fab autoAb cross-reacted with normal mouse (NM) Fab, ssDNA (but not dsDNA), poly(dA,dT), and RNA polymerase I (RPI). Affinity-purified anti-NM IgG Ab isolated from the same 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, but 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 autoAb, induced by immunization with rabbit anti-DNA IgG, were each idiotypically specific for homologous and autologous rabbit anti-ssDNA Fab. Together, these data provide evidence that anti-DNA, anti-RPI and anti-Fab autoAb are linked in a complex, multiple-specific and perhaps regulatory, immune response idiotype network in SLE.