Antibody production in mice deficient for complement receptors 1 and 2 canbe induced by IgG/Ag and IgE/Ag, but not IgM/Ag complexes

Deficiencies in C factors C2, C3, or C4 as well as lack of C receptors 1 an d 2 (CR1/2) lead to impaired Ab production. Classical pathway activation pl ays a major role, as mice deficient in factor B, a key factor in the altern ative pathway, have normal Ab production Abs in complex with their specific Ag are known to feedback regulate the Ab response, and enhanced responses are initiated by IgM, IgE, and IgG, IgM acts via the C system, whereas IgE and Ige can operate independently of C via Fc receptors, Here we have inves tigated whether these isotypes are able to enhance Ab responses in mice lac king CR1/2, SRBC-specific IgM, administered with SRBC, does not enhance Ab responses in these animals. In contrast, 2,4,6-trinitrophenyl-specific IgE and IgG2a, administered with BSA-2,4,6-trinitrophenyl, induce potent Ab res ponses in CR1/2-deficient mice. Additionally, BSA administered with CFA or alum induced strong Ab responses in the absence of CR1/2, These results ind icate that CR1/2 is needed to promote IgM-mediated induction of primary Ab responses, The data also show that the need for CR1/2 can be circumvented b y Abs typical of a secondary immune response forming complexes with Ag or b y conventional adjuvants, presumably mimicking physiological inflammatory r eactions.