Cutting Edge: Identification of the Mouse IgG3 Receptor: Implications for Antibody Effector Function at the Interface Between Innate and Adaptive Immunity

Abstract

Mouse IgG3 appears early in immune responses independently of T cell help and, as such, is an early effector molecule of the immune system. Yet, a specific IgG3 cellular receptor remains undefined. In transfection experiments, mouse FcγRI was clearly able to bind immune complexes of IgG3, whereas mouse FcγRII could not. Furthermore, macrophages from mice expressing FcγRII and FcγRIII but lacking FcγRI were unable to phagocytose IgG3 immune complexes, thus identifying mouse FcγRI as the sole receptor for IgG3 immune complexes. Competition studies demonstrated that monomeric mouse IgG3 could inhibit IgG2a binding to mouse FcγRI with an ID50 ≈10−7 M (fivefold lower than IgG2a). The identification of mouse FcγRI as the IgG3 receptor establishes FcγRI as a participant in events at the interface between innate and adaptive immunity, implying a greater role for this receptor in the development of normal and pathologic immune responses than previously recognized.