Cytokine-Induced Immune Complex Binding To The High-Affinity Igg Receptor, Fc Gamma Ri, In The Presence Of Monomeric Igg

Fc gamma RI is the sole high-affinity immunoglobulin G (IgG) receptor on leukocytes. Its role in immunity and the clearance of opsonized particles has been challenged, as the receptor function may well be hindered by serum IgG. Here, we document immune complex binding by Fc gamma RI to be readily enhanced by cytokine stimulation, whereas binding of monomeric IgG only modestly increased. Enhanced immune complex binding was independent of Fc gamma RI surface expression levels. Fc gamma RI, saturated with prebound IgG, was found capable of effective immune complex binding upon cytokine stimulation. Cytokine-enhanced binding was observed across a variety of immune complexes, including huIgG3- or mIgG2a-opsonized red blood cells, rituximab- or ofatumumab-opsonized B-cell lymphoma, and cetuximab-opsonized glioblastoma cells. This study contributes to our understanding of how Fc gamma RI can participate in the clearance of opsonized particles despite saturation by monomeric IgG. (Blood. 2010;116(24):5327-5333)