Dominant Expression of the Inhibitory FcγRIIB Prevents Antigen Presentation by Murine Plasmacytoid Dendritic Cells

Plasmacytoid dendritic cells (pDCs) are key regulators of the innate immune response, yet their direct role as APCs in the adaptive immune response is unclear. We found that unlike conventional DCs, immune complex (IC) exposed murine pDCs neither up-regulated costimulatory molecules nor activated Ag-specific CD4(+) and CD8(+) T cells. The inability of murine pDCs to promote T cell activation was due to inefficient proteolytic processing of internalized ICs. This defect in the IC processing capacity of pDCs results from a lack of activating Fc gamma R expression (Fc gamma RI, III, IV) and the dominant expression of the inhibitory receptor Fc gamma RIIB. Consistent with this idea, transgenic expression of the activating human Fc gamma RIIA gene, not present in the mouse genome, recapitulated the human situation and rescued IC antigenic presentation capacity by murine pDCs. The selective expression of Fc gamma RIIB by murine pDCs was not strain dependent and was maintained even following stimulation with TLR ligands and inflammatory cytokines. The unexpected difference between the mouse and human in the expression of activating/inhibitory Fc gamma Rs has implications for the role of pDCs in Ab-modulated autoimmunity and anti-viral immunity. The Journal of Immunology, 2009, 183: 7129-7139.