Induction of active immunological hypo/non-responsiveness to C5 in adult C5-deficient DBA/2 mice

Injection of C5-sufficient BALB/c serum rendered DBA/2 mice (C5-deficient) immunologically hypo- or non-responsive to C5. This was indicated by C5-elimination studies in the C5-deficient mice showing similar half-lives for C5 upon single and repeated BALB/c serum injection. Concrete evidence for C5 non-responsiveness came from experiments showing that C5-injected DBA/2 mice were unable to mount an anti-C5 antibody response after active immunization with C5-sufficient serum in Freund's complete adjuvant. C5 hypo/non-responsiveness could be induced in DBA/2 mice via the intravenous as well as the intraperitoneal route, provided the C5-sufficient serum was administered in the very narrow dose range of 10-100 microliters (approximately 0.3-3 micrograms of C5). Upon i.v. C5 injection, C5 non-responsiveness was nearly complete on Day 4 and lasted about 3 weeks. Hyporesponsiveness was still present 6 weeks after serum injection. C3-/C5-depleting cobra venom factor reversed tolerization for C5, at least when applied within 48 hr after i.v. C5 injection. Similarity between the acquired C5 hypo/non-responsiveness of DBA/2 mice and the established C5 tolerance of BALB/c mice was suggested by adoptive cell transfer experiments: spleen cells from naive DBA/2 mice stimulated B cells of C5-sufficient nude mice to produce C5-neutralizing antibodies. In contrast, splenocytes from C5-tolerized DBA/2 mice, like those of BALB/c mice, did not decrease haemolytic C5 levels in C5-sufficient nude mice.