Section of Rheumatology, Department of Medicine, Temple University, USA.
J Autoimmun. 2010 Dec;35(4):368-74. doi: 10.1016/j.jaut.2010.08.001. Epub 2010 Sep 6.
Control of lymphocyte homeostasis is essential to ensure efficient immune responses and to prevent autoimmunity. Splenic marginal zone B cells are important producers of autoantibodies, and are subject to stringent tolerance mechanisms to prevent autoimmunity. In this paper, we explore the role of the Mer tyrosine kinase (Mertk) in regulating autoreactive B cells. This receptor tyrosine kinase serves to bind apoptotic cells, to mediate their phagocytosis, and to regulate subsequent cytokine production. Mice lacking Mertk suffer from impaired apoptotic cell clearance and develop a lupus-like autoimmune syndrome. Here we show that such Mertk-KO mice have expanded numbers of splenic marginal zone B cells. Mertk-KO mice bearing a DNA-specific immunoglobulin heavy-chain transgene (3H9) produced anti-DNA antibodies that appeared to be secreted largely by marginal zone B cells. Finally, Mertk-KO mice developed greater antibody responses after NP-Ficoll immunization than their B6 counterparts. Taken together, our data show that Mertk has a major effect on the development of the marginal zone B-cell compartment. Mertk is also important in establishing DNA-specific B-cell tolerance in 3H9 anti-DNA transgenic mice.
淋巴细胞稳态的控制对于确保有效的免疫反应和预防自身免疫至关重要。脾脏边缘区 B 细胞是自身抗体的重要产生者，并且受到严格的耐受机制的约束，以防止自身免疫。在本文中，我们探讨了 Mer 酪氨酸激酶（Mertk）在调节自身反应性 B 细胞中的作用。该受体酪氨酸激酶用于结合凋亡细胞，介导其吞噬作用，并调节随后的细胞因子产生。缺乏 Mertk 的小鼠表现出凋亡细胞清除受损，并发展出狼疮样自身免疫综合征。在这里，我们表明，这种 Mertk-KO 小鼠具有更多的脾脏边缘区 B 细胞数量。携带 DNA 特异性免疫球蛋白重链转基因（3H9）的 Mertk-KO 小鼠产生了抗 DNA 抗体，这些抗体似乎主要由边缘区 B 细胞分泌。最后，与 B6 对照相比，Mertk-KO 小鼠在 NP-Ficoll 免疫接种后产生了更大的抗体反应。总之，我们的数据表明 Mertk 对边缘区 B 细胞区室的发育有重大影响。Mertk 对于 3H9 抗 DNA 转基因小鼠中 DNA 特异性 B 细胞耐受的建立也很重要。
