The role of Fcgamma receptors on plasmacytoid dendritic cells in antigen presentation and viral immunity

Plasmacytoid DCs (pDCs) are key regulators of the innate immune response, through their copious production of IFNalpha, yet their direct role as antigen presenting cells in the adaptive immune response is unclear. We found that unlike conventional DCs, immune complex (IC) exposed murine pDCs neither upregulated costimulatory molecules nor activated antigen-specific CD4+ and CD8+ T cells. The inability of murine pDCs to promote T cell activation was due to a lack of activating Fcgamma receptor expression (FcyRI, III, IV) and the dominant expression of the inhibitory receptor FcgammaRIIB. Consistent with this idea, transgenic expression of the activating human FcgammaRIIA gene, not present in the mouse genome, rescued IC antigenic presentation capacity by murine pDCs. The selective expression of FcgammaRIIB by murine pDCs lead to inhibition of IFNgamma production in the presence of antibody opsonized virus. We found that viral memory responses in the mouse, a situation that includes the in vivo formation of viral immune complexes, led to similar inhibition of interferon. Thus, the selective expression of FcgammaRIIB by murine pDCs may represent a mechanism by which the unnecessary and potentially injurious production of IFN from pDCs during memory responses is prevented in allowing the previously formed adaptive immune response to proceed.