IMMUNIZATION OF BALB C MICE WITH A MONOCLONAL ANTI-DNA ANTIBODY INDUCES AN ANTIIDIOTYPIC ANTIBODY-REACTIVE WITH A CELL-SURFACE DNA-BINDING PROTEIN/

DNA binds to cell-surface proteins on human and murine leukocytes and induces secretion of the cytokine interleukin 6 (IL-6). Cell-surface D NA binding molecules have been shown to serve as target antigens for t he production of autoantibodies in patients with systemic lupus erythe matosus (SLE), and in lupus-prone mice. Recent studies have demonstrat ed that a subset of anti-anti-DNA antibodies, isolated from patients w ith SLE, are idiotypically related to antibodies reactive with a cell- surface DNA binding molecule. We now report that immunization of norma l mice with a murine monoclonal anti-DNA antibody induces an anti-idio typic response which has reactivity with a cell-surface DNA binding mo lecule. An anti-idiotypic anti-DNA monoclonal antibody (LB17) was isol ated from the spleen of an immunized mouse. This monoclonal antibody b locked the binding of DNA to murine splenocytes and mimicked the funct ional effect of DNA by stimulating the secretion of IL-6. These experi ments provide further evidence for an idiotypic connectivity between a ntibodies to cell-surface DNA binding proteins and anti-DNA antibodies . It is hypothesized that this idiotypic system is part of the network of natural autoantibodies and that its perturbation may give rise to pathogenic antibodies.