FcγRIIA can induce active systemic anaphylaxis. (A) Representative histogram plots of human FcR expression on human blood neutrophils. (B) Representative histogram plots of anti-FLAG mAb (top panel) or preformed mouse polyclonal IgG-immune complexes (bottom panel) binding to CHO transfectants expressing the indicated FLAG-tagged human polymorphic variants of FcγRIIA (H₁₃₁ or R₁₃₁) and FcγRIIIB (NA1, NA2, or SH). (C) Representative expression of FcγRIIA on blood and peritoneal cells from 3KOIIA mice (open histograms) or nontransgenic 3KO littermate controls (filled histograms): T cells (CD3⁺), B cells (CD19⁺), NK cells (DX5⁺/NK1.1⁺), neutrophils (Gr1^hi/CD11b⁺), eosinophils (Gr1^int/SiglecF⁺), basophils (IgE⁺/DX5⁺), and monocytes/macrophages (CD11b⁺/Gr1⁻). (D) Representative expression of FcγRIIA (open histograms) on human blood cells: T cells (CD3⁺), B cells (CD19⁺), NK cells (CD56⁺), neutrophils (CD24⁺), eosinophils (CCR3⁺/CDw125⁺), basophils (FcϵRI⁺/CD203c⁺), and monocytes (CD14⁺); or isotype control (closed histograms). (E-G) Indicated mice were immunized with BSA, (E) in Freunds adjuvant, or (F-G) in alum, challenged with BSA and central temperatures and survival rates were monitored. (E) ASA in FcRγ^−/− (n = 7) and FcRγ^−/−IIA mice (n = 5). (F) ASA in FcRγ^−/− (n = 4) and FcRγ^−/−IIA (n = 5) mice. (G) ASA in FcRγ^−/−IIA mice injected twice with anti-FcγRIIA mAb IV.3 (n = 5) or not (n = 6), before BSA-challenge. FcRγ^−/− mice were used as controls (n = 7). (E-G) Data are represented as mean ± SEM. (A-G) Data are representative of at least 2 independent experiments (*P < .05; **P < .01; ***P < .001).