巴塞尔大学Tobias Derfuss团队近日取得一项新成果。经过不懈努力，他们研制了表达EBV潜伏膜蛋白1的B细胞在中枢神经系统捕获髓鞘抗原，导致脱髓鞘病变形成。2026年1月13日出版的《细胞》杂志发表了这项成果。
在小鼠中，小组观察到病毒感染诱导B细胞浸润到大脑中，独立于表型和特异性，髓磷脂反应性B细胞然后直接从实质中捕获抗原。没有观察到这些装载抗原的B细胞运输到引流淋巴结，没有T细胞的帮助，捕获抗原的B细胞会迅速死亡。CD40L信号或EBV潜伏膜蛋白1 （LMP1）可以覆盖这个检查点，导致B细胞受体和/或抗体依赖性炎症脱髓鞘。在健康人B细胞库中鉴定出髓磷脂反应性B细胞，并在MS患者的大脑亚群中观察到LMP1的表达。这些观察结果可以解释疾病发病率对既往EBV感染的依赖性，以及与脑感染相关的风险增加，并提出可能的治疗策略。
研究人员表示，B细胞耗竭疗法的疗效及其与EB病毒（EBV）的关联暗示了B细胞在多发性硬化症（MS）发病机制中的作用。
附：英文原文
Title: Myelin antigen capture in the CNS by B cells expressing EBV latent membrane protein 1 leads to demyelinating lesion formation
Author: Hyein Kim, Mika Schneider, Yakine Raach, Panajotis Karypidis, Julien Roux, Georgios Perdikaris, Sebastian Holdermann, Laila Kulsvehagen, Anne-Catherine Lecourt, Kerstin Narr, Roman Sankowski, Martin Diebold, Ewelina Bartoszek-Kandler, Josef P. Kapfhammer, Gert Zimmer, Anne-Katrin Prbstel, Marco Prinz, Ludwig Kappos, Nicholas S.R. Sanderson, Tobias Derfuss
Issue&Volume: 2026-01-13
Abstract: The efficacy of B cell depletion therapies, and their association with Epstein-Barr virus (EBV), implicate B cells in the pathogenesis of multiple sclerosis (MS). In mice, we observed that viral infections induce infiltration of B cells into the brain, independent of phenotype and specificity, and that myelin-reactive B cells then capture antigens directly from parenchyma. Trafficking of these antigen-loaded B cells to draining lymph nodes was not observed, and without T cell help, antigen-capturing B cells die rapidly. CD40L signaling or EBV latent membrane protein 1 (LMP1) can override this checkpoint, leading to B cell-receptor- and/or antibody-dependent inflammatory demyelination. Myelin-reactive B cells were identified in the healthy human B cell repertoire, and expression of LMP1 was observed in the brains of a subset of MS patients. These observations can explain the dependency of disease incidence on prior EBV infection, and the increased risk associated with brain infections, and suggest possible treatment strategies.
DOI: 10.1016/j.cell.2025.12.031
Source: https://www.cell.com/cell/abstract/S0092-8674(25)01480-1