STAT‐dependent transciptional regulation of inhibitory Fc gamma RIIb in human monocytes and B cells

Abstract

Fc gamma receptors (FcγR) bind IgG immune complexes and play an important role in the regulation of innate and adaptive immune responses. FcγRIIb mediates negative signaling through the inhibitory motif present in the cytoplasmic domain. Altered expression of FcγRIIb on B cells and monocytes is associated with autoimmune and inflammatory conditions. We observed differential regulation of FCGR2B promoter activity and transcript expression by IL‐4 and IFN‐γ. We investigated the mechanisms involved in the transcriptional regulation of FCGR2B promoter. A putative STAT binding motif is present at position −162 to −154 in the FCGR2B promoter. EMSA experiments with nuclear extracts from human monocytic and B cell lines indicated interaction of STAT1 and STAT4 transcription factors with the FCGR2B promoter probe at this site. Mutation of the putative STAT binding motif within the FCGR2B promoter sequence altered the formation of STAT complexes and downregulated the FCGR2B promoter activity in luciferase assays. Our data suggest that STAT family factors could participate in the transcriptional regulation of the FCGR2B promoter and provide new insight into the modulation of FcγRIIb expression by cytokines during inflammation.