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Jeffrey V. Ravetch
The Rockefeller University
New York, NY

Fc Receptors: Primary Modulators of Antibody Effector Function

Antibody triggered inflammatory responses result from their interaction with a variety of effector pathways. In a number of murine models of anaphylactic, cytotoxic, and immune complex mediated inflammation, IgG Fc receptors have emerged as the primary pathway for transducing the effector capacity of IgG. The cellular activation responses generated in response to FcR crosslinking are modulated by an inhibitory receptor with pleiotropic activities. Among these activities are the ability to regulate calcium signaling by modulating the activity of the Btk family of kinases. The net result of engagement of activation and inhibitory pathways is to provide both threshold requirements and graded responses to stimulation by antibody. The possibility of manipulating the relative affinity of IgG for activation and inhibitory receptors provides the rationale for reengineering the Fc domain of therapeutic antibodies.