The cell-triggering properties of BCR, TCR and FcR depend on structurally related immunoreceptor tyrosine-based activation motifs (ITAMs). FcyRllB have no ITAM and do not trigger cell activation. When coaggregated to BCR, they inhibit B cell activation. We show here that, when coaggregated to these recep tors, FcyRllB inhibit FceRI-, FcyRIIA-, and TCR-dependent cell activation. Inhibition also affected cell activation by single ITAMs, in isolated FcR or TCR subunits. Thesame tyrosine-based inhibitory motif (ITIM), which is highly conserved in murine and human FcyRllB and that was previously shown to inhibit BCR-dependent B cell activation, was required to regulate TCR-and FcR-dependent cell activation. Our findings endow FcyRIIB, and thus IgG antibodies, with general immunoregulatory properties susceptible to act on all ITAM-containing receptors.