Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression
Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression
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DOI：
10.1172/jci36030
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发表时间：
2008-10-01
影响因子：
15.9
通讯作者：
Tedder, Thomas F.
中科院分区：
文献类型：
--
作者：
Matsushita, Takashi;Yanaba, Koichi;Tedder, Thomas F.
EAE是一种小鼠T细胞介导的CNS自身免疫性疾病，用于模拟人类MS病症。B细胞对EAE起始和进展的贡献尚不清楚。在这项研究中，我们已经表明，EAE疾病的开始和进展的差异影响的B细胞从小鼠的消耗，否则完整的免疫系统。在EAE诱导前，CD 20抗体介导的B细胞耗竭显著加重了疾病症状，并增加了致脑炎性T细胞流入CNS。由于在EAE诱导前过继转移脾B10细胞使B细胞耗竭小鼠的EAE正常化，因此产生IL-10的罕见CD 1d（hi）CD 5（+）调节性B细胞亚群（B10细胞）耗竭导致症状严重程度增加。虽然调节性B10细胞的转移在早期EAE启动期间最有效，但它们在疾病进展期间没有明显作用。相反，B细胞耗竭在EAE疾病进展期间显著抑制症状。具体而言，B细胞是产生CNS自身抗原特异性CD 4（+）T细胞和疾病进展过程中致脑炎T细胞进入CNS所必需的。这些结果证明了B细胞在EAE免疫发病机制中的相互调节作用。因此，B细胞耗竭治疗自身免疫的治疗效果可能取决于疾病起始和发病过程中这些相反的B细胞活性的相对贡献和时间。
EAE is a mouse T cell-mediated autoimmune disease of the CNS used to model the human condition MS. The contributions of B cells to EAE initiation and progression are unclear. In this study, we have shown that EAE disease initiation and progression are differentially influenced by the depletion of B cells from mice with otherwise intact immune systems. CD20 antibody-mediated B cell depletion before EAE induction substantially exacerbated disease symptoms and increased encephalitogenic T cell influx into the CNS. Increased symptom severity resulted from the depletion of a rare IL-10-producing CD1d(hi)CD5(+) regulatory B cell subset (B10 cells), since the adoptive transfer of splenic B10 cells before EAE induction normalized EAE in B cell-depleted mice. While transfer of regulatory B10 cells was maximally effective during early EAE initiation, they had no obvious role during disease progression. Rather, B cell depletion during EAE disease progression dramatically suppressed symptoms. Specifically, B cells were required for the generation of CD4(+)T cells specific for CNS autoantigen and the entry of encephalitogenic T cells into the CNS during disease progression. These results demonstrate reciprocal regulatory roles for B cells during EAE immunopathogenesis. The therapeutic effect of B cell depletion for the treatment of autoimmunity may therefore depend on the relative contributions and the timing of these opposing B cell activities during the course of disease initiation and pathogenesis.