The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses.
The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven adaptive immune responses.
复制标题
免疫受体衔接蛋白DAP12抑制了B淋巴细胞驱动的适应性免疫反应。
DOI：
10.1084/jem.20101623
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发表时间：
2011-08-01
期刊：
影响因子：
--
通讯作者：
Shibuya A
中科院分区：
文献类型：
--
作者：
Nakano-Yokomizo T;Tahara-Hanaoka S;Nakahashi-Oda C;Nabekura T;Tchao NK;Kadosaki M;Totsuka N;Kurita N;Nakamagoe K;Tamaoka A;Takai T;Yasui T;Kikutani H;Honda S;Shibuya K;Lanier LL;Shibuya A
缺乏功能性DAP12的人和小鼠B细胞是高反应性的，DAP12与Mair-II(CD300d)一起负向调节B细胞的活性。DAP12是一种基于酪氨酸的免疫受体激活基序适配蛋白，参与自然杀伤细胞和髓系细胞介导的先天免疫。我们发现，DAP12缺失的小鼠B细胞和来自Nasu-Hakola病患者的B细胞在抗IgM或CpG刺激下表现出促进增殖的作用。髓系免疫球蛋白样受体(Mair)II(CD300d)是DAP12相关的免疫受体。与DAP12缺陷的B细胞一样，MAIR-II缺陷的B细胞也具有高反应性。将Mair-II胞外区与DAP12直接偶联的嵌合受体表达到DAP12缺陷或Mair-II缺陷的B细胞中，可抑制B细胞受体(BCR)介导的增殖。Mair-II-DAP12嵌合受体在BCR刺激后募集含有SH2结构域的蛋白酪氨酸磷酸酶1(SHP-1)。DAP12基因缺陷小鼠对自身抗原的血清抗体升高，对T细胞依赖和T细胞非依赖抗原的体液免疫反应增强。因此，DAP12偶联的Mair-II负性调节B细胞介导的获得性免疫反应。
Human and mouse B cells lacking functional DAP12 are hyperresponsive, and DAP12 works with MAIR-II (CD300d) to negatively regulate B cell activity. 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.
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影响因子：
30.5
作者：
Hamerman, JA;Tchao, NK;Lanier, LL
通讯作者：
Lanier, LL
影响因子：
8.7
作者：
Lanier LL
通讯作者：
Lanier LL
影响因子：
4.4
作者：
Hamerman, Jessica A.;Jarjoura, Vessica R.;Lanier, Lewis L.
通讯作者：
Lanier, Lewis L.
DOI：
10.1006/bbrc.2001.5539
发表时间：
2001-09-14
影响因子：
3.1
作者：
Luo, K;Zhang, WP;Cao, XT
通讯作者：
Cao, XT
影响因子：
4.4
作者：
Chung, DH;Humphrey, MB;Daws, MR
通讯作者：
Daws, MR