INTERPLAY BETWEEN VIRUSES AND B CELLS IN THE PATHOGENESIS OF MULTIPLE SCLEROSIS.

多发性硬化（MS）是一种慢性进行性自身免疫性神经系统疾病，是西方国家最常见的脱髓鞘疾病。虽然在提供新的治疗策略方面取得了重大进展，但MS的确定性致病因子的鉴定已被证明是难以捉摸的。已知许多因素参与其中，包括UVB水平、维生素D和人类内源性逆转录病毒（HERV）。然而，最近的研究表明，EB病毒（Epstein-Barr Virus，EBV）是MS的最大危险因素，重要的是，它们在MS的发病机制中的作用尚不清楚，本项目旨在了解EBV、B细胞分化状态和先天免疫是如何协同作用触发HERV-W在B细胞中的再激活的。此后，利用MS患者脑脊液中的B细胞，我们将探索这些因素如何协同作用产生针对病毒蛋白和MS自身免疫靶点（包括髓鞘）的交叉反应抗体。通过确定病毒是如何导致MS发病的，我们将为该疾病开辟急需的新的治疗和预防途径，主要目的是控制触发原因，而不仅仅是修改后期的免疫损伤。

Multiple sclerosis (MS) is a chronic progressive autoimmune neurological disease and themost common demyelinating disorder in Western countries. Although significant progresshas been made in providing new therapeutic strategies, identification of definitive triggersfor MS has proven elusive. Many factors are known to be involved, including UVB levels andvitamin-D and Human endogenous retrovirus (HERV). However, recent studies have shownEpstein-Barr Virus (EBV) is the single biggest risk factor for MS Importantly, theircontribution to the pathogenesis of MS remains unknown.In this project we aim to understand how EBV, B cell differentiation status and innateimmunity co-operate to trigger reactivation of HERV-W in B cells. Thereafter, using B cellsfrom the cerebrospinal fluid of MS patients, we will explore how these factors co-operateto generate cross-reactive antibodies targeting both viral proteins and MS autoimmunetargets, including myelin. By pinning down how the viruses contribute tothe pathogenesis of MS, we will open-up badly needed new treatment andprevention avenues for the disease, principally aimed at controlling the triggering causesrather than just modifying the later immune damage.