Epstein–Barr virus (EBV) is an aetiologic risk factor for the development of multiple sclerosis (MS). However, the role of EBV-infected B cells in the immunopathology of MS is not well understood. Here we characterized spontaneous lymphoblastoid cell lines (SLCLs) isolated from MS patients and healthy controls (HC) ex vivo to study EBV and host gene expression in the context of an individual’s endogenous EBV. SLCLs derived from MS patient B cells during active disease had higher EBV lytic gene expression than SLCLs from MS patients with stable disease or HCs. Host gene expression analysis revealed activation of pathways associated with hypercytokinemia and interferon signalling in MS SLCLs and upregulation of forkhead box protein 1 (FOXP1), which contributes to EBV lytic gene expression. We demonstrate that antiviral approaches targeting EBV replication decreased cytokine production and autologous CD4⁺ T cell responses in this ex vivo model. These data suggest that dysregulation of intrinsic B cell control of EBV gene expression drives a pro-inflammatory, pathogenic B cell phenotype that can be attenuated by suppressing EBV lytic gene expression.

EB 病毒 (EBV) 是多发性硬化症 (MS) 发展的病因学危险因素。然而，EBV 感染的 B 细胞在 MS 免疫病理学中的作用尚不清楚。在这里，我们对从多发性硬化症患者和健康对照 (HC) 离体分离的自发性淋巴母细胞系 (SLCL) 进行了表征，以研究个体内源性 EBV 背景下的 EBV 和宿主基因表达。源自疾病活动期 MS 患者 B 细胞的 SLCL 比源自疾病稳定的 MS 患者或 HC 的 SLCL 具有更高的 EBV 裂解基因表达。宿主基因表达分析揭示了 MS SLCL 中与高细胞因子血症和干扰素信号传导相关的通路的激活以及叉头盒蛋白 1 (FOXP1) 的上调，这有助于 EBV 裂解基因的表达。我们证明，在该离体模型中，针对 EBV 复制的抗病毒方法减少了细胞因子的产生和自体 CD4 ⁺ T 细胞反应。这些数据表明，B 细胞对 EBV 基因表达的内在控制失调会导致促炎、致病性 B 细胞表型，而这种表型可以通过抑制 EBV 裂解基因表达来减弱。