Efficient IgG-mediated suppression of primary antibody responses in Fc gamma receptor-deficient mice

IgG antibodies can suppress more than 99% of the antibody response against the antigen to which they bind. This is used clinically to prevent rhesus-n egative (Rh-) women from becoming immunized against Rh+ erythrocytes from t heir fetuses. The suppressive mechanism is poorly understood, but it has be en proposed that IgG/erythrocyte complexes bind to the inhibitory Pc recept or for IgG (Fc gamma RIIB) on the B cell surface, thereby triggering negati ve signals that turn off the B cell. We show that IgG induces the same degr ee of suppression of the response to sheep erythrocytes in animals lacking the known IgG-binding receptors Fc gamma RIIB, Fc gamma RI + III, Fc gamma RI + IIB + III,and FcRn (the neonatal Pc receptor) as in wild-type animals. Reinvestigation of the ability of F(ab')(2) fragments to suppress antibody responses demonstrated that they were nearly as efficient as intact IgG. I n addition, monoclonal IgE also was shown to be suppressive. These findings suggest that IgG inhibits antibody responses through Fc-independent mechan isms, most likely by masking of antigenic epitopes, thereby preventing B ce lls from binding and responding to antigen. In agreement with this, we show that T cell priming is not abolished by passively administered IgG. The re sults have implications for the understanding of in vivo regulation of anti body responses and Rh prophylaxis.