Batoulis Helena, Wunsch Marie, Birkenheier Johannes, Rottlaender Andrea, Gorboulev Valentin, Kuerten Stefanie
Department of Anatomy I, University of Cologne, Joseph-Stelzmann-Str. 9, 50931 Cologne, Germany.
Department of Anatomy and Cell Biology, University of Wuerzburg, Koellikerstr. 6, 97070 Wuerzburg, Germany.
Clin Immunol. 2015 May;158(1):47-58. doi: 10.1016/j.clim.2015.03.009. Epub 2015 Mar 18.
In multiple sclerosis (MS) lymphoid follicle-like aggregates have been reported in the meninges of patients. Here we investigated the functional relevance of B cell infiltration into the central nervous system (CNS) in MP4-induced experimental autoimmune encephalomyelitis (EAE), a B cell-dependent mouse model of MS. In chronic EAE, B cell aggregates were characterized by the presence of CXCL13(+) and germinal center CD10(+) B cells. Germline transcripts were expressed in the CNS and particularly related to TH17-associated isotypes. We also observed B cells with restricted VH gene usage that differed from clones found in the spleen. Finally, we detected CNS-restricted spreading of the antigen-specific B cell response towards a myelin and a neuronal autoantigen. These data imply the development of autonomous B cell-mediated autoimmunity in the CNS in EAE - a concept that might also apply to MS itself.
在多发性硬化症（MS）患者的脑膜中已报道存在类淋巴滤泡聚集物。在此，我们研究了B细胞浸润到中枢神经系统（CNS）在MP4诱导的实验性自身免疫性脑脊髓炎（EAE）中的功能相关性，EAE是一种依赖B细胞的MS小鼠模型。在慢性EAE中，B细胞聚集物的特征是存在CXCL13(+)和生发中心CD10(+) B细胞。胚系转录本在CNS中表达，且特别与TH17相关的同种型有关。我们还观察到VH基因使用受限的B细胞，它们与脾脏中发现的克隆不同。最后，我们检测到抗原特异性B细胞反应在CNS中针对髓鞘和神经元自身抗原的局限性扩散。这些数据表明在EAE中CNS内存在自主的B细胞介导的自身免疫——这一概念可能也适用于MS本身。
