A Restricted Role for FcγR in the Regulation of Adaptive Immunity

By their interaction with IgG immune complexes, FcγR and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficientmice, IgG downstream effectorfunctions are often impaired, as well as adaptive immunity. Based on a variety of model systems using FcγR-knockout mice, it has been concluded that FcγRs are also key regulators of innate and adaptive immunity; however, several of the model systems underpinning these conclusions suffer from flawed experimental design. To address this issue, we generated a novel mouse model deficient for all FcγRs (FcγRI/II/III/IV −/− mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effectorpathways were impaired, adaptive immuneresponses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like FcγRIIb-deficient mice, FcγRI/II/III/IV −/− mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating FcγRs in the modulation of the adaptive immuneresponse in vivo. We conclude that FcγRs are downstream IgG effectormolecules with a restricted role in the ontogenyand maintenance of the immunesystem, as well as the regulation of adaptive immunity.