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

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