Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease.
Meningeal Infiltration of the Spinal Cord by Non-Classically Activated B Cells is Associated with Chronic Disease Course in a Spontaneous B Cell-Dependent Model of CNS Autoimmune Disease.
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DOI：
10.3389/fimmu.2015.00470
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发表时间：
2015
影响因子：
7.3
通讯作者：
Kerfoot SM
中科院分区：
文献类型：
--
作者：
Dang AK;Tesfagiorgis Y;Jain RW;Craig HC;Kerfoot SM
我们在中枢神经系统（CNS）自身免疫的B细胞依赖自发模型中描述了脊髓的B细胞浸润，该模型在一定比例具有髓鞘少突胶质细胞糖蛋白特异性T细胞和B细胞受体突变的小鼠中发展。我们发现，虽然男性更容易患病，但女性更有可能患上慢性疾病，而不是单相疾病。采用组织学和流式细胞术观察脊髓B细胞浸润情况。CD4+ T细胞浸润在整个白质和部分灰质中普遍存在。B细胞几乎完全局限于脑膜，经常聚集在一起，让人想起人类多发性硬化症。这些团簇通常在白质病变附近发现，它们的存在与慢性疾病病程有关。通过组织学对这些簇进行了广泛的研究，但没有发现淋巴滤泡的特征，包括T细胞和B细胞在不同区域的组织，CD35+滤泡树突状细胞或生发中心。多数簇B细胞为IgD+，几乎没有类别转换的证据。与此一致的是，从脊髓中分离的B细胞具有naïve/记忆CD38hi CD95lo表型。然而，与淋巴结B细胞相比，它们是CD62Llo和CD80hi，这表明它们至少部分被激活并启动呈递抗原。因此，如果脑膜B细胞在自身免疫中参与中枢神经系统病理，则滤泡分化不是致病机制所必需的。
We characterized B cell infiltration of the spinal cord in a B cell-dependent spontaneous model of central nervous system (CNS) autoimmunity that develops in a proportion of mice with mutant T and B cell receptors specific for myelin oligodendrocyte glycoprotein. We found that, while males are more likely to develop disease, females are more likely to have a chronic rather than monophasic disease course. B cell infiltration of the spinal cord was investigated by histology and FACs. CD4+ T cell infiltration was pervasive throughout the white and in some cases gray matter. B cells were almost exclusively restricted to the meninges, often in clusters reminiscent of those described in human multiple sclerosis. These clusters were typically found adjacent to white matter lesions and their presence was associated with a chronic disease course. Extensive investigation of these clusters by histology did not identify features of lymphoid follicles, including organization of T and B cells into separate zones, CD35+ follicular dendritic cells, or germinal centers. The majority of cluster B cells were IgD+ with little evidence of class switch. Consistent with this, B cells isolated from the spinal cord were of the naïve/memory CD38hi CD95lo phenotype. Nevertheless, they were CD62Llo and CD80hi compared to lymph node B cells suggesting that they were at least partly activated and primed to present antigen. Therefore, if meningeal B cells contribute to CNS pathology in autoimmunity, follicular differentiation is not necessary for the pathogenic mechanism.