摘要

The presence of B lymphocyte-associated oligoclonal immunoglobulins in the cerebrospinal fluid is a classic hallmark of multiple sclerosis (MS). The clinical efficacy of anti-CD20 therapies supports a major role for B lymphocytes in MS development. Although activated oligoclonal populations of pathogenic B lymphocytes are able to traffic between the peripheral circulation and the central nervous system (CNS) in patients with MS, molecular players involved in this migration have not yet been elucidated. In this study, we demonstrated that activated leukocyte cell adhesion molecule (ALCAM/CD166) identifies subsets of proinflammatory B lymphocytes and drives their transmigration across different CNS barriers in mouse and human. We also showcased that blocking ALCAM alleviated disease severity in animals affected by a B cell-dependent form of experimental autoimmune encephalomyelitis. Last, we determined that the proportion of ALCAM+ B lymphocytes was increased in the peripheral blood and within brain lesions of patients with MS. Our findings indicate that restricting access to the CNS by targeting ALCAM on pathogenic B lymphocytes might represent a promising strategy for the development of next-generation B lymphocyte-targeting therapies for the treatment of MS.

译文

脑脊液中 B 淋巴细胞相关寡克隆免疫球蛋白的存在是多发性硬化症 (MS) 的典型特征。Anti-CD20 疗法的临床疗效支持了 B 淋巴细胞在 MS 发育中的主要作用。尽管在 MS 患者中,活化的致病 B 淋巴细胞寡克隆群体能够在外周循环和中枢神经系统 (CNS) 之间流动, 参与这种迁移的分子分子尚未阐明。在这项研究中,我们证明了激活的白细胞细胞粘附分子 (ALCAM/CD166) 识别促炎 B 淋巴细胞的亚群,并驱动它们在小鼠和人类的不同 CNS 屏障上的迁移。我们还展示了阻断 ALCAM 减轻了受 b细胞依赖性实验性自身免疫性脑脊髓炎影响的动物的疾病严重程度。最后,我们确定 ALCAM B 淋巴细胞在多发性硬化症患者外周血和脑部病变中的比例增加。我们的研究结果表明,通过针对致病性 B 淋巴细胞的 ALCAM 来限制进入 CNS 可能是开发下一代 B 淋巴细胞靶向治疗 MS 的一个有希望的策略。

Lymphocyte

免疫 淋巴细胞 临床研究术语
概述  :  

淋巴细胞是白细胞的一种,是机体内数量大而体积最小的白细胞,是机体免疫系统重要组成成分。淋巴细胞具有免疫活性,它们可以通过本身的杀伤作用或产生抗体如免疫球蛋白等来防御、杀伤或杀灭机体内的外源致病因子如病菌、肿瘤细胞等。 分类及区别 根据淋巴细胞的发生来源、形态结构、表面标志和免疫功能等方面的不同,可分为T细胞、B细胞和NK细胞三类。 1.T淋巴细胞能够直接攻击侵入人体的微生物和体内的肿瘤细胞等,发挥细胞免疫功能。B淋巴细胞在

Lymphocyte 英 [’limfəsait] 美 [’limfəsait]

释    义    n.淋巴细胞,淋巴球

同根词    lymphoma n. 淋巴瘤    

lymphoid adj. 淋巴的;淋巴样的

例    句    Individual lymph nodes consist of lymphocytes clustered in lymphoid follicles and reticuloendothelial cells lining nodal sinuses.单个淋巴结由聚集在淋巴滤泡内的淋巴细胞和排列在淋巴窦内的网状内皮细胞组成。

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