The same tyrosine-based inhibition motif, in the intracytoplasmic domain of Fc gamma RIIB, regulates negatively BCR-, TCR-, 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.
Daëron
M
M
Laboratoire d'Immunologie Cellulaire et Clinique, Institut National de la Santé et de la Recherche Médicale U255, Institut Curie, Paris, France.
Latour
S
S
Malbec
O
O
Espinosa
E
E
Pina
P
P
Pasmans
S
S
Fridman
W H
WH
D000595:Amino Acid Sequence; D000818:Animals; D001491:Basophils; D015536:Down-Regulation / Q000235:genetics; D006636:Histamine Release / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D051381:Rats; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011961:Receptors, Fc / Q000378:metabolism*; D017455:Receptors, IgE / Q000378:metabolism; D017452:Receptors, IgG / Q000737:chemistry* / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000737:chemistry
D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D011961:Receptors, Fc; D017455:Receptors, IgE; D017452:Receptors, IgG; D012701:Serotonin; D014443:Tyrosine