B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis.
B cell antigen presentation is sufficient to drive neuroinflammation in an animal model of multiple sclerosis.
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DOI：
10.4049/jimmunol.1402236
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发表时间：
2015-06-01
期刊：
影响因子：
--
通讯作者：
Wu GF
中科院分区：
文献类型：
--
作者：
Parker Harp CR;Archambault AS;Sim J;Ferris ST;Mikesell RJ;Koni PA;Shimoda M;Linington C;Russell JH;Wu GF
B 细胞越来越被认为是多发性硬化症 (MS) 发病机制中不可或缺的一部分，部分原因是 B 细胞耗竭疗法的成功。使用实验性自身免疫性脑脊髓炎 (EAE) 探索了导致中枢神经系统 (CNS) 炎症性脱髓鞘的多种 B 细胞依赖性机制，EAE 是一种 CD4 T 细胞依赖性多发性硬化症 (MS) 动物模型。虽然 B 细胞抗原呈递被认为可以调节 EAE 期间的 CNS 炎症，但缺乏直接证据表明 B 细胞可以独立支持 EAE 中 CD4 T 细胞的抗原特异性自身免疫反应。使用新开发的 MHCII 体内条件表达小鼠模型，我们之前报道，当 B 细胞是唯一的抗原呈递细胞时，致脑炎 CD4 T 细胞无法诱导 EAE。在此，我们发现 B 细胞与树突状细胞合作增强髓磷脂少突胶质细胞糖蛋白 (MOG) 免疫导致的 EAE 严重程度。此外，增加 MOG 特异性 B 细胞的前体频率，但不添加可溶性 MOG 特异性抗体，足以驱动仅通过 B 细胞表达 MHCII 的小鼠中的 EAE。这些数据支持一个模型，其中中枢神经系统自身免疫期间抗原特异性 B 细胞的扩增放大了 B 和 CD4 T 细胞之间的同源相互作用，并且有能力在疾病后期独立驱动神经炎症。
B cells are increasingly regarded as integral to the pathogenesis of multiple sclerosis (MS) in part due to the success of B cell depletion therapy. Multiple B cell-dependent mechanisms contributing to inflammatory demyelination of the central nervous system (CNS) have been explored using experimental autoimmune encephalomyelitis (EAE), a CD4 T cell-dependent animal model for multiple sclerosis (MS). While B cell antigen presentation has been suggested to regulate CNS inflammation during EAE, direct evidence that B cells can independently support antigen-specific autoimmune responses by CD4 T cells in EAE is lacking. Using a newly developed murine model of in vivo conditional expression of MHCII, we previously reported that encephalitogenic CD4 T cells are incapable of inducing EAE when B cells are the sole antigen presenting cell. Herein we find that B cells cooperate with dendritic cells to enhance EAE severity resulting from myelin oligodendrocyte glycoprotein (MOG) immunization. Further, increasing the precursor frequency of MOG-specific B cells, but not addition of soluble MOG-specific antibody, is sufficient to drive EAE in mice expressing MHCII by B cells alone. These data support a model in which expansion of antigen-specific B cells during CNS autoimmunity amplifies cognate interactions between B and CD4 T cells and have the capacity to independently drive neuro-inflammation at later stages of disease.
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DOI：
10.1016/j.bbadis.2010.07.008
发表时间：
2011-02
影响因子：
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作者：
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