Role of PIR-B in autoimmune glomerulonephritis.
PIR-B, an inhibitory receptor expressed on murine B cells and myeloid cells, regulates humoral and cellular immune responses via its constitutive binding to the ligand, MHC class I molecules, on the same cells (cis) or on different cells (trans). Although it has been speculated that PIR-B is important for maintaining peripheral tolerance, PIR-B single deficiency does not cause overt autoimmune diseases. Recently, however, the combination of its deficiency with the Fas lpr mutation was found to result in augmented production of autoantibodies such as IgG rheumatoid factor and anti-DNA IgG, leading to glomerulonephritis in mice. Although the precise molecular mechanism for the overall scenario is unclear, PIR-B was found to suppress TLR9-mediated production of naturally autoreactive antibodies by innate B cells or B-1 cells by inhibiting the activation of Bruton's tyrosine kinase. Thus, PIR-B is an important regulator of innate immunity mediated by TLR9 in B-1 cells, which can otherwise provoke autoimmunity when overactivated.
Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan. tostakai@idac.tohoku.ac.jp
Toshiyuki
T
Takai
Akira
A
Nakamura
Shota
S
Endo
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis / Q000276:immunology; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000276:immunology* / Q000503:physiopathology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology / Q000378:metabolism; D007108:Immune Tolerance; D007113:Immunity, Innate; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011971:Receptors, Immunologic / Q000737:chemistry / Q000172:deficiency* / Q000502:physiology*; D012217:Rheumatoid Factor / Q000096:biosynthesis / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D019014:fas Receptor / Q000172:deficiency* / Q000276:immunology
D000974:Antibodies, Antinuclear; C491899:Fas protein, mouse; D015395:Histocompatibility Antigens Class I; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D019014:fas Receptor; D012217:Rheumatoid Factor; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625951:Btk protein, mouse