title: The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses.
abstract: DAP12, an immunoreceptor tyrosine-based activation motif-bearing adapter protein, is involved in innate immunity mediated by natural killer cells and myeloid cells. We show that DAP12-deficient mouse B cells and B cells from a patient with Nasu-Hakola disease, a recessive genetic disorder resulting from loss of DAP12, showed enhanced proliferation after stimulation with anti-IgM or CpG. Myeloid-associated immunoglobulin-like receptor (MAIR) II (Cd300d) is a DAP12-associated immune receptor. Like DAP12-deficient B cells, MAIR-II-deficient B cells were hyperresponsive. Expression of a chimeric receptor composed of the MAIR-II extracellular domain directly coupled to DAP12 into the DAP12-deficient or MAIR-II-deficient B cells suppressed B cell receptor (BCR)-mediated proliferation. The chimeric MAIR-II-DAP12 receptor recruited the SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) after BCR stimulation. DAP12-deficient mice showed elevated serum antibodies against self-antigens and enhanced humoral immune responses against T cell-dependent and T cell-independent antigens. Thus, DAP12-coupled MAIR-II negatively regulates B cell-mediated adaptive immune responses.
authors: Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki 305-8575, Japan.
authors: Takako
authors: T
authors: Nakano-Yokomizo
authors: Satoko
authors: S
authors: Tahara-Hanaoka
authors: Chigusa
authors: C
authors: Nakahashi-Oda
authors: Tsukasa
authors: T
authors: Nabekura
authors: Nadia K
authors: NK
authors: Tchao
authors: Momoko
authors: M
authors: Kadosaki
authors: Naoya
authors: N
authors: Totsuka
authors: Naoki
authors: N
authors: Kurita
authors: Kiyotaka
authors: K
authors: Nakamagoe
authors: Akira
authors: A
authors: Tamaoka
authors: Toshiyuki
authors: T
authors: Takai
authors: Teruhito
authors: T
authors: Yasui
authors: Hitoshi
authors: H
authors: Kikutani
authors: Shin-ichiro
authors: S
authors: Honda
authors: Kazuko
authors: K
authors: Shibuya
authors: Lewis L
authors: LL
authors: Lanier
authors: Akira
authors: A
authors: Shibuya
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus; D008060:Lipodystrophy / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010009:Osteochondrodysplasias / Q000276:immunology*; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism; D055607:Receptors, Natural Killer Cell / Q000172:deficiency / Q000276:immunology*; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D013344:Subacute Sclerosing Panencephalitis / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D055607:Receptors, Natural Killer Cell; D019056:Receptors, Polymeric Immunoglobulin; D011993:Recombinant Fusion Proteins; C484963:Tyrobp protein, mouse; C517261:myeloid-associated Ig-like receptor, mouse; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; C509248:Ptpn6 protein, mouse