重症肌无力胸腺肌样细胞缺乏DAF在胸腺内启动AChR异常免疫应答

Myasthenia gravis (MG) is a typical autoimmune disease of central nervous system. It is well-considered that the pathogenesis of MG is closely associated with thymus. But so far, it remains unclear that why and how MG thymus initiates an autoimmune response to AChR. Accumulating data indicate MG thymus contain cellular components required to initiate an autoimmune response to AChR: myoid cells expressing acetylcholine receptor (AChR) antigen, professional antigen presenting cells-dendritic cell (DC) that can efficiently present autoimmunogenic epitopes, autoreactive T cells, and germinal center(GC) in which B cells proliferate and secrete antibody. Newly study indicates myoid cell in MG thymus lack the expression of complement regulator-DAF. Therefore, we presume myoid cell in MG thymus is vulnerable to complement-mediated damage because of low-expression of complement regulator. AChR can be exposed, captured and presented to autoreactive T cells, finally helping B cells secreting antibody in thymic GC, and initiating an autoimmune response to AChR. Our study will discuss the relationship among thymic myoid cells, thymic DCs,DAF,GC and MG from the level of MG patients as well as in vitro and in vivo, which is of significance in unfolding intrathymic pathogenesis of MG.

重症肌无力（MG）是典型的神经系统自身免疫性疾病。目前公认MG的发生与胸腺密切相关。但迄今为止，MG患者胸腺为何、如何启动异常免疫应答尚不明确。众多研究表明，MG患者胸腺在结构上具备激发异常免疫应答的条件：表达乙酰胆碱受体(AChR)的肌样细胞，专职的抗原递呈细胞-树突状细胞（DC），自身反应性T细胞以及B细胞增殖、产生抗体的场所-异位生发中心（GC）。新近的研究发现MG患者肌样细胞缺乏补体调节因子DAF的表达。因此，我们推测MG患者胸腺肌样细胞因缺乏补体调节因子-DAF的保护，易受补体攻击、损伤，使原本在胸腺内隐蔽的AChR抗原暴露，被树突状细胞摄取、提呈抗原信息给AChR反应性T细胞，在胸腺GC中辅助B细胞产生抗体，引起针对AChR的异常免疫应答。本研究将从MG患者及体内、体外水平集中探讨胸腺肌样细胞、胸腺树突状细胞、DAF及GC与MG之间的关系，对揭示MG胸腺发病机制具有重要意义。