FcγR dependent mechanisms of cytotoxic, agonistic, and neutralizing antibody activities

Given the widespread use of antibodies of the immunoglobulin G (IgG) class as cytotoxic, immunomodulatory, and neutralizing agents in the therapy of malignant, infectious, and autoimmune diseases, understanding the molecular and cellular mechanisms responsible for their therapeutic activity is of major importance. While Fc gamma receptors (Fc gamma R) have well-appreciated roles as effectors of cytotoxic IgG activity, it has only recently become clear that the functionality of immunomodulatory and neutralizing IgG preparations also depends on cellular Fc gamma Rs. Here, we review current models of IgG activity in infectious and inflammatory settings, and examine the importance of cell type-specific expression of Fc gamma Rs in determining functional outcome. We discuss how this knowledge may be used to improve the activity of therapeutic antibody preparations and outline important areas of focus for future research.