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。认为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细胞必须伴随凋亡而被清除。Bcl-2家族蛋白调节程序性细胞死亡，并可能在淋巴细胞的选择中发挥重要作用。应用流式细胞仪检测人淋巴细胞Bcl-2、Bcl-x、Bax、巴克和Bim的表达。Bcl-2在CD 4 ^+8^+（DP）胸腺细胞和CD 19 ^+38^+扁桃体淋巴细胞（GC B细胞）中表达下调。在DP胸腺细胞中，共表达CD 69的细胞上调Bcl-2，表明Bcl-2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阳性（SP）细胞，而在CD 69 ^+ DP胸腺细胞中的表达水平低于CD 69 ^- DP胸腺细胞。Bim在DP胸腺细胞中表达较低，但在GCB细胞亚群中表达较高。SP胸腺细胞Bim和Bax表达高于DP胸腺细胞。在外周血淋巴细胞（PBL）中，CD 8 ^+ T细胞表达的Bcl-x水平是CD 4 ^+ T细胞的10倍，而两个亚群表达的Bcl-2水平相似。PBL中巴克低表达，Bim表达缺失，提示Bcl-2家族的其他成员不仅参与胸腺T细胞的发育，而且参与生殖中心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