Distinct Expression and Function of FcεRII in Human B Cells and Monocytes

FceRII is a multifunctional low-affinity IgER that is involved in the pathogenesis of allergic, inflammatory, and neoplastic diseases. Although discrepancies in FceRII-mediated functions are being increasingly recognized, the consequences of FceRII activation are not completely understood. In this study, we evaluated the expression of FceRII on human blood cells and found that it was primarily expressed on monocytes and B cells. Although IL-4 promoted expression of the FceRIIb isoform on B cells and monocytes, the expression of the FceRIIa isoform was not dependent on IL-4. Furthermore, FceRII predominantly bound allergen–IgE complexes on B cells but not on monocytes. FceRII-mediated allergen–IgE complex uptake by B cells directed Ags to MHC class II–rich compartments. FceRII-bearing monocytes and B cells expressed high levels of the FceRII sheddase a disintegrin and metalloproteinase 10, which implies that they are important sources of soluble FceRII. Moreover, we identified that IgE immune complex stimulation of FceRII activated intracellular tyrosine phosphorylation via Syk in B cells but not in monocytes. Importantly, FceRII-mediated signaling by allergen–IgE immune complexes increased IFN-γ production in B cells of allergic patients during the build-up phase of allergen-specific immunotherapy. Together, our results demonstrate that FceRII mediates cell type-dependent function in allergic reactions. In addition, the results identify a novel allergen–IgE complex/FceRII/Syk/IFN-γ pathway in allergic responses and suggest that FceRII may play a role in regulating allergic reactions via modulating IFN-γ production in B cells.