Cytokine-regulated expression and inhibitory function of Fc RIIB1 and -B2 receptors in human dendritic cells

Dendritic cells (DCs) capture immune complexes (ICs) via Fc receptors for immunoglobulin G (Fc R)II and elicit antigen presentation and protective antitumoral immune response in mice. Two protocols are commonly used to differentiate human monocyte-derived DCs in vitro. They associate granulocyte macrophage-colony stimulating factor with interleukin (IL)-4 or IL-13. In this study, we first assessed the ability of the two types of DCs to initiate an immune response against an IC-linked antigen. We evidenced that IL-4 and IL-13 DCs display comparable lymphocyte stimulatory capacity and similar lifetimes. We next characterized Fc RIIs expressed by pure populations of circulating myeloid DCs, IL-4, and IL-13 DCs. We highlighted the expression of Fc RIIA, -B1, and -B2 by pure populations of circulating blood DC antigen-1 myeloid DCs and IL-4 and IL-13 DCs. Moreover, IL-4 and IL-13 DCs displayed greater Fc RIIB expression than monocytes but a comparable Fc RIIA. We next investigated the Fc RIIB mechanism of action. We evidenced that deleting Fc RIIB increased the ability of IC-pulsed DCs to stimulate autologous lymphocytes. Fc RIIB acted by lowering IC uptake, surface expression of costimulation molecules, and cytokine release. Finally, the balance between activating Fc RIIA/inhibitory Fc RIIB (B1 B2) could be modulated in vitro by inflammation mediators. By lowering Fc RIIB expression without significantly affecting Fc RIIA, prostaglandin E2 (PGE-2) appeared to be a major regulator of this balance. IL-1 and tumor necrosis factor were also found to potentiate PGE-2 action. Altogether, our results evidence an inhibitory role for Fc RIIB in human DCs and provide an easy way to possibly improve in vitro the induction of immune response against IC-linked antigen. J. Leukoc. Biol. 79: 000–000; 2006.