Fc gamma Receptor IIb Strongly Regulates Fc gamma Receptor-Facilitated T Cell Activation by Dendritic Cells

Fc gamma R ligation by Ag-Ab immune complexes (IC) not only mediates effective Ag uptake, but also strongly initiates dendritic cell (DC) maturation, a requirement for effective T cell activation. Besides the activating Fc gamma RI, Fc gamma RIII, and Fc gamma RIV, the inhibitory Fc gamma RIIb is expressed on DCs. It is unclear how the ratio between signals from the activating Fc gamma R and the inhibitory Fc gamma RIIb determines the outcome of Fc gamma R ligation on DCs. By microarray analysis, we compared the transcriptomes of steady state and IC-activated bone marrow-derived wild-type (WT) DCs expressing all Fc gamma R or DCs expressing only activating Fc gamma R (Fc gamma RIIb knockout [KO]) or only the inhibitory Fc gamma RIIb (FcR gamma-chain KO). In WT DCs, we observed a gene expression profile associated with effective T cell activation, which was absent in FcR gamma-chainKO, but strikingly more pronounced in Fc gamma RIIb KO bone marrow-derived DCs. These microarray results, confirmed at the protein level for many cytokines and other immunological relevant genes, demonstrate that the transcriptome of IC-activated DCs is dependent on the presence of the activating Fc gamma R and that the modulation of the expression of the majority of the genes was strongly regulated by Fc gamma RIIb. Our data suggest that Fc gamma RIIb-deficient DCs have an improved capacity to activate naive T lymphocytes. This was confirmed by their enhanced Fc gamma R-dependent Ag presentation and in vivo induction of CD8(+) T cell expansion compared with WT DCs. Our findings underscore the potency of Fc gamma R ligation on DCs for the effective induction of T cell immunity by ICs and the strong regulatory role of Fc gamma RIIb. The Journal of Immunology, 2012, 189: 92-101.