What is the antigen that induce myasthenia gravis? : the specificity of anti-AchR antibody in the patient of myasthenia gravis

重症肌无力是由抗AchR抗体引起的自身免疫性疾病。据说自身免疫性疾病与自身反应性T细胞相互作用。在T细胞发育过程中，自身反应性T细胞必须随着细胞的凋亡而被删除。BCL-2家族蛋白调控细胞程序性死亡，可能在淋巴细胞的选择中发挥重要作用。用流式细胞仪检测人淋巴细胞中Bcl2、Bclx、Bax、Bak和Bim的表达。CD4+8+(DP)胸腺细胞和CD19+38+扁桃体淋巴细胞(GC B细胞)中bcl2表达下调。在DP胸腺细胞中，共表达CD69的细胞上调了Bcl2，提示Bcl2的作用是促进阳性选择的Dp细胞的存活。出乎意料的是，Bcl-x在DP细胞中的表达水平高于单一阳性(SP)细胞，而在CD69^+DP胸腺细胞中的表达水平低于CD69^-DP胸腺细胞。Bim在DP胸腺细胞中低表达，但在GCB细胞亚群中高表达。BIM和Bax在SP胸腺细胞中的表达高于DP胸腺细胞。在外周血淋巴细胞(PBL)中，CD8^+T细胞表达的Bclx水平是CD4^+T细胞的10倍，而两者表达的Bcl2水平相近。Bak在PBL中低表达，Bim在PBL中不表达。提示不仅Bcl2家族成员参与了胸腺T细胞的发育和生发中心B细胞的亲和力成熟

Myasthenia gravis is auto-immune disease because of anti-AchR antibody. It is said that auto-immune disease is interacted with auto-reactive T cell. Auto-reactive T cell must be deleted with apoptosis in T cell development. Bcl-2 family proteins regulate programmed cell death, and may play an important role in the selection of lymphocytes. We investigated the expression of Bcl-2, Bcl-x, Bax, Bak and Bim in human lymphocytes using flow-cytometry. Bcl-2 was down-regulated in CD4^+8^+ (DP) thymocytes and CD19^+38^+ tonsillar lymphocytes (GC B cells). Among DP thymocytes, cells co-expressing CD69 up-regulated Bcl-2, suggesting that the role of Bcl-2 is promoting survival of positively selected DP cells. Unexpectedly, the expression level of Bcl-x was higher in DP cells than in Single Positive (SP) cells and in CD69^+ DP thymocytes it was lower than in CD69^- DP thymocytes. Expression of Bim was low in DP thymocytes but high in a subset of GCB cells. Bim and Bax were expressed more highly in SP than in DP thymocytes. Among peripheral blood lymphocytes (PBL), CD8^+ T cells expressed a〜10 fold higher level of Bcl-x than CD4^+ T cells while both subsets expressed similar levels of Bcl-2. Bak expression was low and Bim expression was absent in PBL.These results suggest that not only Bcl-2 but other members of the Bcl-2 family are involved in T cell development in the thymus and affinity maturation of B cells in the germinal center