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

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 Fc gamma RI was clearly able to bind immune complexes of IgG3, whereas mouse Fc gamma RII could not, Furthermore, macrophages from mice expressing Fc gamma RII and Fc gamma RIII but lacking Fc gamma RI were unable to phagocytose IgG3 immune complexes, thus identifying mouse Fc gamma RI as the sole receptor for IgG3 immune complexes, Competition studies demonstrated that monomeric mouse IgC3 could inhibit IgG2a binding to mouse Fc gamma RI with an ID50 approximate to 10(-7) M (fivefold lower than IgG2a). The identification of mouse Fc gamma RI as the IgG3 receptor establishes Fc gamma RI 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.