Fcγ Receptors Inhibit Mouse and Human Basophil Activation

Besides high-affinity IgE receptors (Fc epsilon RI), human basophils express activating (Fc gamma RIIA) and inhibitory (Fc gamma RIIB) low-affinity IgG receptors. IgG receptors (Fc gamma R) were also found on mouse basophils, but not identified. We investigated in this study Fc gamma R and the biological consequences of their engagement in basophils of the two species. We found the following: 1) that mouse basophils also express activating (Fc gamma RIIIA) and inhibitory (Fc gamma RIIB) low-affinity FcgR; 2) that activating Fc gamma R can activate both human and mouse basophils, albeit with different efficacies; 3) that negative signals triggered by inhibitory Fc gamma R are dominant over positive signals triggered by activating Fc gamma R, thus preventing both human and mouse basophils from being activated by IgG immune complexes; 4) that the coengagement of Fc epsilon RI with inhibitory and activating Fc gamma R results in a Fc gamma RIIB-dependent inhibition of IgE-induced responses of both human and mouse basophils; 5) that Fc gamma RIIB has a similar dominant inhibitory effect in basophils from virtually all normal donors; and 6) that IL-3 upregulates the expression of both activating and inhibitory Fc gamma R on human basophils from normal donors, but further enhances Fc gamma RIIB-dependent inhibition. Fc gamma R therefore function as a regulatory module, made of two subunits with antagonistic properties, that prevents IgG-induced and controls IgE-induced basophil activation in both mice and humans. The Journal of Immunology, 2012, 189: 2995-3006.