A Restricted Role for Fc?R in the Regulation of Adaptive Immunity.

ABSTRACT: By their interaction with IgG immune complexes, Fc?R and complement link innate and adaptive immunity, showing functional redundancy. In complement-deficient mice, IgG downstream effector functions are often impaired, as well as adaptive immunity. Based on a variety of model systems using Fc?R-knockout mice, it has been concluded that Fc?Rs 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 Fc?Rs (Fc?RI/II/III/IV-/- mice). These mice displayed normal development and lymphoid and myeloid ontogeny. Although IgG effector pathways were impaired, adaptive immune responses to a variety of challenges, including bacterial infection and IgG immune complexes, were not. Like Fc?RIIb-deficient mice, Fc?RI/II/III/IV-/- mice developed higher Ab titers but no autoantibodies. These observations indicate a redundant role for activating Fc?Rs in the modulation of the adaptive immune response in vivo. We conclude that Fc?Rs are downstream IgG effector molecules with a restricted role in the ontogeny and maintenance of the immune system, as well as the regulation of adaptive immunity.

SUBMITTER: Fransen MF 

PROVIDER: S-EPMC5896742 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature