A Model for the Anti-Inflammatory Activity of 2,6-Sialylated Fc. In mice, 2,6-sialylated Fc present in IVIG binds to SIGN-R1 on splenic macrophages. This results in secretion of unidentified soluble anti-inflammatory mediators, which bind to effector macrophages at tissue sites of inflammation. The effector macrophages increase surface expression of the inhibitory FcγRIIB receptor. FcγRIIB competes for binding of antibody–antigen complexes to activating FcγR and increases the threshold concentration of antibody–antigen complexes required for inflammation. In humans, the receptor for 2,6-sialylated Fc is DC-SIGN and the regulatory cells are dendritic cells that are not restricted to the spleen.