Inhibitory Fcγ receptor is required for the maintenance of tolerance through distinct mechanisms.

The inhibitory Fc gamma R Fc gamma RIIB is widely expressed on B cells, dendritic cells (DCs), and myeloid effector cells and modulates a variety of Ab-driven in vivo functions. Although it has been established that Fc gamma RIIB plays an important role in the maintenance of peripheral tolerance, the responsible cell-specific Fc gamma RIIB expression remains to be determined. In this study, we generated mice with selective deletion of Fc gamma RIIB in B cells, DCs, and myeloid effector cells and evaluated these novel strains in models of tolerance and autoimmune diseases. Our results demonstrate that mice with selective deletion of Fc gamma RIIB expression in B cells and DCs have increased Ab and T cell responses, respectively, and display enhanced susceptibility to disease in distinct models, suggesting that Fc gamma RIIB expression in distinct cellular populations contributes to the maintenance of peripheral tolerance through different mechanisms.