Human and mouse FcγRs, despite sharing names and CDs, differ in their IgG subclass binding specificities. Mice express four FcγRs: FcγRI, FcγRIIB, FcγRIII, and FcγRIV, with FcγRIIB being the sole inhibitory receptor, carrying an intrinsic ITIM motif like its human counterpart. FcγRIV is mouse-specific and absent in humans. FcγRI binds IgG2a, IgG2b, and IgG3, but not IgG1, with high affinity for IgG2a. FcγRIIB and FcγRIII differ in their ITIM vs. ITAM associations, binding IgG1, IgG2a, and IgG2b with low affinities. FcγRIV binds IgG2a and IgG2b with high affinities. Notably, FcγRIIB, FcγRIII, and FcγRIV, but not FcγRI, also bind IgE, albeit with low affinity, making FcγRI a 'strict' IgG receptor. Unlike mice, humans express FcγRIIA, FcγRIIC, and FcγRIIIB.