Regulated expression of FcyR in human dendritic cells controls cross-presentation of antigen-antibody complexes

Receptors for IgG (Fc gamma R) expressed in dendritic cells (DCs) influence the initiation of Ab-mediated immunity. Dynamic variations in Fc gamma R expression allow DCs to adjust their capacity to capture Ab-opsonized Ag. The current paradigm predicts a progressive decline in Fc gamma R-mediated phagocytic function upon DC maturation. Surprisingly, we find that expression of the phagocytic receptor Fc gamma RIIa is preserved in immature and mature DCs at comparable levels with macrophages. Moreover, phagocytosis of antigenic peptides directed to Fc gamma RIIa on DCs leads to dramatic increases in Ag cross-presentation and T cell activation. In immature DCs, high expression of inhibitory Fc gamma RIIb correlates with decreased uptake and cross-presentation of Ab-Ag complexes. In contrast, engagement of Fc gamma RIIb is not associated with changes in cross-presentation in mature DCs. We provide evidence that Fc gamma RIIb expression is patently reduced in mature DCs, an effect that is modulated by treatment with cytokines. The regulated expression of activating and inhibitory Fc gamma Rs in DCs emerges as a critical checkpoint in the process of Ag uptake and cross-presentation.