Allergen-specific IgG antibody signaling through FcγRIIb promotes food tolerance

Background Patients with food allergy produce high-titer IgE antibodies that bind to mast cells through FceRI and trigger immediate hypersensitivity reactions on antigen encounter. Food-specific IgG antibodies arise in the setting of naturally resolving food allergy and accompany the acquisition of food allergen unresponsiveness in oral immunotherapy. Objective In this study we sought to delineate the effects of IgG and its inhibitory Fc receptor, FcγRIIb, on both de novo allergen sensitization in naive animals and on established immune responses in the setting of pre-existing food allergy. Methods Allergen-specific IgG was administered to mice undergoing sensitization and desensitization to the model food allergen ovalbumin. Cellular and molecular mechanisms were interrogated by using mast cell– and FcγRIIb-deficient mice. The requirement for FcγRII in IgG-mediated inhibition of human mast cells was investigated by using a neutralizing antibody. Results Administration of specific IgG to food allergy–prone IL4raF709 mice during initial food exposure prevented the development of IgE antibodies, T H 2 responses, and anaphylactic responses on challenge. When given as an adjunct to oral desensitization in mice with established IgE-mediated hypersensitivity, IgG facilitated tolerance restoration, favoring expansion of forkhead box protein 3–positive regulatory T cells along with suppression of existing T H 2 and IgE responses. IgG and FcγRIIb suppress adaptive allergic responses through effects on mast cell function. Conclusion These findings suggest that allergen-specific IgG antibodies can act to induce and sustain immunologic tolerance to foods.