Mast cells and basophils are selectively activated in vitro and in vivo through CD200R3 in an IgE-Independent manner
Mast cells and basophils are selectively activated in vitro and in vivo through CD200R3 in an IgE-Independent manner
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DOI：
10.4049/jimmunol.179.10.7093
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发表时间：
2007-11-15
影响因子：
4.4
通讯作者：
Karasuyama, Hajime
中科院分区：
文献类型：
--
作者：
Kojima, Toshiyuki;Obata, Kazushige;Karasuyama, Hajime
肥大细胞和嗜碱性粒细胞参与宿主对病原体的防御系统，并参与过敏性疾病的发展。虽然IgE依赖性反应通过Fc ε RI对这些细胞已被广泛研究，很少有人知道的细胞表面分子，这些细胞选择性表达，并参与其激活通过IgE非依赖性机制。我们最近建立了两个单克隆抗体，反应特异性与小鼠肥大细胞和嗜碱性粒细胞，其中一个选择性耗尽嗜碱性粒细胞时，在体内给药。生化和流式细胞仪分析显示，这两种单克隆抗体特异性识别CD 200 R样蛋白，CD 200 R3，但不识别其他CD 200 R家族成员。CD 200 R3以二硫键连接的二聚体形式存在，与其他CD 200 R不同，主要在肥大细胞和嗜碱性粒细胞上表达，并与带有ITAM的衔接子DAP 12相关。CD 200 R3与mAb的交联诱导肥大细胞的脱粒和嗜碱性粒细胞中细胞因子IL-4的体外产生。体内给予非消耗性mAb以CD 200 R3依赖性方式引起全身和局部过敏反应。这些结果表明，CD 200 R3作为活化受体的肥大细胞和嗜碱性粒细胞调节IgE非依赖性免疫反应的抑制性受体CD 200 R，类似于NK细胞上表达的配对受体的合作。
Mast cells and basophils have been implicated in the host defense system against pathogens and in the development of allergic disorders. Although IgE-dependent responses via Fc epsilon RI on these cells have been extensively studied, little is known about cell surface molecules that are selectively expressed by these cells and engaged in their activation via an IgE-independent mechanism. We have recently established two mAbs that reacted specifically with murine mast cells and basophils, and one of them selectively depleted basophils when administered in vivo. Biochemical and flow cytometric analyses revealed that both mAbs specifically recognized a CD200R-like protein, CD200R3, but not other CD200R family members. CD200R3 existed as a disulfide-linked dimer, unlike other CD200Rs, and was expressed on mast cells and basophils primarily in association with an ITAM-bearing adaptor DAP12. Cross-linking of CD200R3 with the mAbs induced degranulation in mast cells and production of the cytokine IL-4 in basophils in vitro. Administration of the nondepleting mAb in vivo elicited systemic and local anaphylaxis in a CD200R3-dependent manner. These results suggest that CD200R3 functions as an activating receptor on mast cells and basophils to regulate IgE-independent immune responses in cooperation with an inhibitory receptor CD200R, similar to the paired receptors expressed on NK cells.