B细胞亚群平衡在多发性硬化发病机制中的作用

多发性硬化(MS)是常见的神经系统自身免疫性疾病，T细胞一直被认为在MS发病中起重要作用，但特异性针对T细胞的临床治疗始终没得到满意效果。相反MS患者治疗过程中偶然清除B细胞却得到出乎意料的好疗效。提示我们重新审视B细胞在发病过程中的重要作用。最新的研究及我们的前期工作初步表明B细胞以非抗体依赖的方式参与MS发病，与T细胞相似，B细胞也可以根据其所分泌的细胞因子分为不同亚型。致病性B细胞和调节性B细胞在MS发病过程中表现完全相反。而目前我们对B细胞还所知甚少。为此本项目围绕着B细胞亚群平衡在MS发病机制中的作用展开，以空间和时间为轴，阐述B细胞亚群如何分化（lncRNA, mirRNA的调控）、B细胞如何调控免疫系统（与T细胞、单核巨噬细胞的关系）、如何迁移（对血脑屏障的作用）以及B细胞对中枢神经系统的影响。以临床发现-基础研究-临床应用的转化医学模式探索以B细胞为靶点的治疗MS的新方法。

Multiple sclerosis (MS) is a kind of common autoimmune disease involved in nerve system. T cell has been considered to play very important role in MS. However no satisfied results achieved in clinical treatment focused on T cells. Contrary to expectation, good curative effect of MS patients got from treatment of occasional clear-off B cells. These facts told us that we should not ignore the role of B cells during the mechanism of MS. Latest studies and our pre-work showed that B cells played an antibody independent role in MS. Similar to T cells, B cells could also be divided into different subsets according to the cytokines they secreted. The effector B cells have totally different effect from regulatory B cells. Unfortunately, we still have little knowledge about B cells. Thus, our project will carry out revolving round the balance of B subsets in the mechanism of MS. According to the sequence of time and place, the follow schemes will be clarified: 1, the differentiation of B cell subsets (the regulation of lncRNA and mirRNA); 2, How do B cells control the immune system (such as the relationship with T cells, monocytes and macrophages); 3, How do B cells migrate into blood brain barrier; and 4, the influence of B cells on the central never system. Following the translational medicine mode, i.e. clinical found – fundamental discoveries – clinical application, we will explore new methods focused on B cells to treat MS patients.