IgG3-mediated enhancement of the antibody response is normal in Fc7RI-deficient mice

Antibodies, administered together with their specific antigen, can feedback-regulate antibody responses to this antigen. IgG1, IgG2a and IgG2b enhance antibody responses to soluble protein antigens. This effect is primarily mediated by FcRs as enhancement is impaired in FcR gamma(-/-) mice, reported to lack Fc gamma RI and Fc gamma RIII because of deletion of the common FcR gamma chain. Also IgG3 can enhance antibody responses. However, this effect is unperturbed in FcR gamma(-/-) mice but severely impaired in complement-depleted animals and in animals lacking complement receptor 1 and 2. Although this argues against involvement of Fc gamma Rs, FcR gamma(-/-) mice may express one-fifth of the normal levels of Fc gamma RI and, in addition, Fc gamma RI has been suggested to bind IgG3. We re-investigated the dependence of IgG3-mediated enhancement on Fc gamma Rs using a mouse strain selectively lacking Fc gamma RI and found that IgG3-mediated enhancement is completely normal. Unlike IgE and IgG2a, which are both thought to enhance T-cell proliferation via FcR-mediated antigen presentation, IgG3 was a poor enhancer of T-cell proliferation both in vivo and in vitro. These findings argue against a significant involvement of Fc gamma Rs in IgG3-mediated enhancement of antibody responses and support our previous conclusion that complement plays a major role.