FcγRIV deletion reveals its central role for IgG2a and IgG2b activity in vivo

Cellular Fc gamma receptors are essential for IgG-dependent effector functions in vivo. There is convincing evidence that selective activating Fc gamma receptors are responsible for the activity of individual IgG subclasses. Thus, IgG1 activity is absent in Fc gamma RIII-deficient mice, and several studies suggest that the activity of the most potent IgG subclasses, IgG2a and IgG2b, might be dependent on either individual or a combination of activating Fc gamma Rs. To study the role of individual activating Fc gamma Rs for IgG subclass activity, we generated an Fc gamma RIV-deficient mouse and showed that a variety of IgG2a- and IgG2b- dependent effector functions are impaired in the absence of this activating Fc gamma receptor in models of autoimmunity and antibody-dependent cellular cytotoxicity.