Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ 85013, USA.
Exp Neurol. 2010 Jan;221(1):136-45. doi: 10.1016/j.expneurol.2009.10.015. Epub 2009 Oct 29.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) thought to be primarily mediated by T cells. However, emerging evidence supports an important role for B cells in the pathogenesis and inhibition of MS. Glatiramer acetate (GA), a Food and Drug Administration-approved drug for the treatment of MS, has a good safety profile. But GA's mechanism of action in MS is still elusive. In this study, we showed that B cells from GA-treated mice increased production of IL-10 and reduced expression of co-stimulatory molecules viz.: CD80 and CD86. B cells from GA-treated mice also diminished proliferation of myelin oligodendrocyte glycoprotein (MOG(35-55)) specific T cells. Purified B cells transferred from GA-treated mice suppressed experimental autoimmune encephalomyelitis (EAE) in recipient mice compared with B cells transferred from mice treated with PBS or ovalbumin. The treatment effect of GA in EAE was abrogated in B cell-deficient mice. Transfer of B cells from GA-treated mice inhibited the proliferation of autoreactive T cells as well as the development of Th1 and Th17 cells but promoted IL-10 production in recipient mice. The number of peripheral CD11b(+) macrophages in recipient mice also decreased after transfer of B cells from GA-treated mice; however, the number of dendritic cells and regulatory T cells remained unaltered. These results suggest that B cells are important to the protective effects of GA in EAE.
多发性硬化症（MS）是一种中枢神经系统（CNS）自身免疫性疾病，被认为主要由 T 细胞介导。然而，新出现的证据支持 B 细胞在 MS 的发病机制和抑制中起重要作用。聚甘酯（GA）是一种经美国食品和药物管理局批准用于治疗 MS 的药物，具有良好的安全性。但 GA 在 MS 中的作用机制仍不清楚。在这项研究中，我们表明，用 GA 治疗的小鼠的 B 细胞增加了白细胞介素 10（IL-10）的产生，并降低了共刺激分子 CD80 和 CD86 的表达。用 GA 治疗的小鼠的 B 细胞也减少了髓鞘少突胶质细胞糖蛋白（MOG(35-55)）特异性 T 细胞的增殖。与从用 PBS 或卵清蛋白治疗的小鼠中转移的 B 细胞相比，从 GA 治疗的小鼠中转移的纯化 B 细胞可抑制受体小鼠的实验性自身免疫性脑脊髓炎（EAE）。在 B 细胞缺陷型小鼠中，GA 在 EAE 中的治疗效果被消除。从 GA 治疗的小鼠中转移的 B 细胞抑制了自身反应性 T 细胞的增殖以及 Th1 和 Th17 细胞的发育，但促进了受体小鼠中白细胞介素 10（IL-10）的产生。受体小鼠外周血中 CD11b（+）巨噬细胞的数量也在从 GA 治疗的小鼠中转移 B 细胞后减少；然而，树突状细胞和调节性 T 细胞的数量保持不变。这些结果表明 B 细胞对 GA 在 EAE 中的保护作用很重要。
