Induction of an immune response to a self antigen

The question has been addressed whether the endogenous B cell population of a mouse can be induced to secrete antibodies specific for a self antigen present in serum. The antigen studied was the fifth component of mouse complement (C5). Nude BALB/c mice which are C5 sufficient were used as a source of potentially C5-reactive B cells and endogenous serum C5 provided the antigenic stimulus. We purposely avoided immunization with C5 in adjuvant. T cells from C5-deficient mice which lack this component in serum and are therefore not tolerant of C5 were injected into nude mice as a source of T cell help for anti-C5 reactive B cells. Control groups received T cells from C5-sufficient euthymic donors, which are tolerant of C5. Initiation of a response to C5 was monitored by testing the hemolytic function of serum. Reduction of C5-dependent hemolysis was observed in sera of mice which had received T cells from C5-deficient donors. Recipients of T cells from C5-sufficient donors maintained normal hemolytic complement levels throughout the test period of 45 days. Reduction of functional complement levels correlated with the presence of immune complexes of anti-C5/C5. C5-specific antibodies were mainly IgG1 and carried the IgG1 allotype of BALB/c providing unequivocal evidence that they were derived from the endogenous B cell population of the C5-sufficient host.