Modulation of immunoglobulin (Ig)E-mediated systemic anaphylaxis by low-affinity Fc receptors for IgG

It is widely accepted that immunoglobulin (Ig)E triggers immediate hypersensitivity responses by activating a cognate high-affinity receptor, Fc epsilon RI, leading to mast cell degranulation with release of vasoactive and proinflammatory mediators. This apparent specificity, however, is complicated by the ability of IgE to bind with low affinity to Fc receptors for IgG, Fc gamma RII and III. We have addressed the in vivo significance of this interaction by studying IgE-mediated passive systemic anaphylaxis in Fc gamma R-deficient mice. Mice deficient in the inhibitory receptor for IgG, Fc gamma RIIB, display enhanced IgE-mediated anaphylactic responses, whereas mice deficient in an IgG activation receptor, Fc gamma RIII, display a corresponding attenuation of IgE-mediated responses. Thus, in addition to modulating IgG-triggered hypersensitivity responses, Fc gamma RII and III on mast cells are potent regulators of IgE-mediated responses and reveal the existence of a regulatory pathway for IgE triggering of effector cells through IgG Fc receptors that could contribute to the etiology of the atopic response.