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Infectious Disorders - Drug Targets
(Formerly Current Drug Targets - Infectious Disorders)
ISSN (Print): 1871-5265
ISSN (Online): 2212-3989
VOLUME: 12
ISSUE: 3
DOI: 10.2174/187152612800564455









Role of Inhibitory BCR Co-Receptors in Immunity

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Author(s): Takeshi Tsubata
Pages 181-190 (10)
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.
Keywords:
B cell, antibody response, autoimmune disease, FcR, CD22, Siglec, immunoreceptor tyrosine-based inhibition motifs (ITIMs), cytoplasmic, autoimmune diseases, glycoproteins, glycolipids, sialic acids, FcγRIIB, genetic studies, rheumatoid arthritis
Affiliation:
Laboratory of Immunology, Tokyo Medical and Dental University Graduate School of Biomedical Sciences, 1-5-45 Yushima, Bunkyo-ku, 113-8510 Tokyo, Japan.