title: Role of inhibitory BCR co-receptors in immunity.
abstract: B lymphocytes (B cells) express a variety of membrane molecules containing immunoreceptor tyrosine-based inhibition motifs (ITIMs) in the cytoplasmic region such as FcγRIIB, FCRLs, CD22, mouse Siglec-G/human Siglec-10, PECAM-1, mouse PIR-B/human LIRB1 and LIRB2PD-1 and CD72. When phosphorylated, ITIMs in these molecules recruit and activate phosphatases such as SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1), SHP-2, SH2 domain- containing inositol 5-phosphatase 1 (SHIP1) and SHIP2 depending on receptors. These phosphatases then negatively regulate B cell antigen receptor (BCR) signaling. Because of their ability to inhibit BCR signaling, these ITIMcontaining molecules are called inhibitory BCR co-receptors. Studies on mice deficient in an inhibitory co-receptor have demonstrated that the inhibitory co-receptors regulate B cell development, antibody responses and development of autoimmune diseases. Moreover, polymorphisms in some inhibitory co-receptors such as FcγRIIB, FCRL3 and CD72 are associated with autoimmune diseases, suggesting a crucial role of inhibitory co-receptor polymorphisms in the regulation of autoimmune diseases. The ligands for inhibitory co-receptors regulate their inhibitory activity by inducing co-ligation of the co-receptors with BCR or some other regulatory mechanisms. Inhibitory co-receptors and their ligands are therefore good targets for controlling antibody responses and autoimmune diseases.
authors.affiliation: Laboratory of Immunology, Tokyo Medical and Dental University Graduate School of Biomedical Sciences, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, Japan. tsubata.imm@mri.tmd.ac.jp
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tsubata
mesh_terms: D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D003593:Cytoplasm / Q000276:immunology; D006801:Humans; D007109:Immunity; D008024:Ligands; D051379:Mice; D010766:Phosphorylation; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology
chemical_list: D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D051918:Sialic Acid Binding Ig-like Lectin 2