THE SAME TYROSINE-BASED INHIBITION MOTIF, IN THE INTRACYTOPLASMIC DOMAIN OF FC-GAMMA-RIIB, REGULATES NEGATIVELY BCR-DEPENDENT, TCR-DEPENDENT, AND FCR-DEPENDENT CELL ACTIVATION

The cell-triggering properties of BCR, TCR and FcR depend on structurally related immunoreceptor tyrosine-based activation motifs (ITAMs). Fc gamma RIIB 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 receptors, Fc gamma RIIB inhibit Fc epsilon RI-, Fc gamma RIIA-, and TCR-dependent cell activation, Inhibition also affected cell activation by single ITAMs, in isolated FcR or TCR subunits, The same tyrosine-based inhibitory motif (ITIM), which is highly conserved in murine and human Fc gamma RIIB 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 Fc gamma RIIB, and thus IgG antibodies, with general immunoregulatory properties susceptible to act on all ITAM-containing receptors.