1. The same tyrosine-based inhibition motif, in the intra-cytoplasmic domain of FcγRIIB, regulates negatively BCR-, TCR-, and FcR-dependent cell activation
- Author
-
Suzanne G.M.A. Pasmans, Odile Malbec, Wolf H. Fridman, Sylvain Latour, Marc Daëron, Patrick Pina, and Eric Espinosa
- Subjects
Serotonin ,Molecular Sequence Data ,Immunology ,Receptors, Antigen, T-Cell ,Down-Regulation ,Receptors, Antigen, B-Cell ,chemical and pharmacologic phenomena ,Receptors, Fc ,Biology ,Lymphocyte Activation ,Histamine Release ,Mice ,Immunoreceptor tyrosine-based activation motif ,Tumor Cells, Cultured ,Animals ,Humans ,Immunology and Allergy ,Amino Acid Sequence ,Tyrosine ,Receptor ,Mice, Inbred BALB C ,Receptors, IgE ,T-cell receptor ,Receptors, IgG ,breakpoint cluster region ,Molecular biology ,Basophils ,Rats ,Infectious Diseases ,Cytoplasm ,Mice, Inbred DBA ,Cell activation ,Immunoreceptor tyrosine-based inhibitory motif - Abstract
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.
- Full Text
- View/download PDF