The identification of key mechanisms and molecules involved in tertiary lymphoid organ formation in the central nervous system in MP4-induced experimental autoimmune encephalomyelitis

多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性炎症性疾病，被认为是自身免疫性疾病。当T细胞的作用被广泛研究时，B细胞才刚刚开始引起人们的重视。最近的研究表明，B细胞在继发性进展性MS患者的脑膜中组织成淋巴滤泡样结构，我们已经在B细胞依赖的小鼠mp4诱导的实验性自身免疫性脑脊髓炎（EAE）中鉴定和功能表征了类似的第三系淋巴器官（TLO）。本研究的目的是确定mp4免疫C57BL/6小鼠小脑B细胞聚集和TLO形成的关键机制和分子。在Aim 1中，将对非和弥漫性B细胞浸润、B细胞聚集和TLO进行RNA微阵列检测，并将数据与B细胞非依赖型髓鞘少突胶质细胞糖蛋白（MOG）：35-55模型和次级淋巴器官（SLO）中CNS浸润的表达谱进行比较。指定标记物的表达将通过qRT-PCR和免疫组织化学进行确认。为了将结果初步翻译为MS设置，我们还将在MS脑切片中搜索包含/不包含B细胞聚集体/滤泡的最有希望的分子。目的2将研究淋巴组织诱导剂（LTi）细胞和表达TH17的podoplanin细胞对MP4模型中TLO形成的贡献。

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) and supposed to be of autoimmune nature. While the role of T cells has been extensively studied, B cells have just begun to attract major attention. It was recently shown that B cells organize themselves into lymphoid follicle-like structures in the meninges of patients with secondary progressive MS and we have identified and functionally characterized similar tertiary lymphoid organs (TLO) in the B cell-dependent murine MP4-induced experimental autoimmune encephalomyelitis (EAE). The aim of this proposal is to identify key mechanisms and molecules involved in B cell aggregation and TLO formation in the cerebellum of MP4-immunized C57BL/6 mice. In Aim 1 RNA microarrays will be performed on non- and diffuse B cell infiltrates, B cell aggregates and TLO and the data will be compared to the expression profiles of CNS infiltrates in the B cell-independent myelin oligodendrocyte glycoprotein (MOG):35-55 model and of secondary lymphoid organs (SLO). The expression of designated markers will be confirmed by qRT-PCR and immunohistochemistry. In an attempt to perform an initial translation of the results to the setting of MS we will also search for the most promising molecules on MS brain sections that contain/do not contain B cell aggregates/follicles. Aim 2 will study the contribution of lymphoid tissue inducer (LTi) cells and podoplanin expressing TH17 cells to TLO formation in the MP4 model.