The association of Epstein‐Barr virus infection with CXCR3+ B‐cell development in multiple sclerosis: impact of immunotherapies,European Journal of Immunology

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The association of Epstein‐Barr virus infection with CXCR3+ B‐cell development in multiple sclerosis: impact of immunotherapies
European Journal of Immunology ( IF 4.5 ) Pub Date : 2020-11-05 , DOI: 10.1002/eji.202048739
Jamie van Langelaar ₁ , Annet F Wierenga-Wolf ₁ , Johnny P A Samijn ₂ , Caroline J M Luijks ₁ , Theodora A Siepman ₃ , Pieter A van Doorn ₃ , Andrew Bell ₄ , Menno C van Zelm ₅ , Joost Smolders _{1,

3,

6} , Marvin M van Luijn ₁

Affiliation

Epstein–Barr virus (EBV) infection of B cells is associated with increased multiple sclerosis (MS) susceptibility. Recently, we found that CXCR3‐expressing B cells preferentially infiltrate the CNS of MS patients. In chronic virus‐infected mice, these types of B cells are sustained and show increased antiviral responsiveness. How EBV persistence in B cells influences their development remains unclear. First, we analyzed ex vivo B‐cell subsets from MS patients who received autologous bone marrow transplantation (n = 9), which is often accompanied by EBV reactivation. The frequencies of nonclass‐switched and class‐switched memory B cells were reduced at 3–7 months, while only class‐switched B cells returned back to baseline at 24–36 months posttransplantation. At these time points, EBV DNA load positively correlated to the frequency of CXCR3⁺, and not CXCR4⁺ or CXCR5⁺, class‐switched B cells. Second, for CXCR3⁺ memory B cells trapped within the blood of MS patients treated with natalizumab (anti‐VLA‐4 antibody n = 15), latent EBV infection corresponded to enhanced in vitro formation of anti‐EBNA1 IgG‐secreting plasma cells under GC‐like conditions. These findings imply that EBV persistence in B cells potentiates brain‐homing and antibody‐producing CXCR3⁺ subsets in MS.

中文翻译：

爱泼斯坦-巴尔病毒感染与多发性硬化症中 CXCR3+ B 细胞发育的关联：免疫疗法的影响

B 细胞的爱泼斯坦-巴尔病毒 (EBV) 感染与多发性硬化 (MS) 易感性增加有关。最近，我们发现表达 CXCR3 的 B 细胞优先浸润 MS 患者的 CNS。在慢性病毒感染的小鼠中，这些类型的 B 细胞持续存在并表现出增强的抗病毒反应能力。B 细胞中 EBV 的持久性如何影响其发育尚不清楚。首先，我们分析了接受自体骨髓移植的 MS 患者的离体 B 细胞亚群（n= 9)，这通常伴随着 EBV 重新激活。非类别转换和类别转换记忆 B 细胞的频率在 3-7 个月时降低，而只有类别转换 B 细胞在移植后 24-36 个月恢复到基线水平。在这些时间点，EBV DNA 负载与 CXCR3 ⁺的频率正相关，而不是 CXCR4 ⁺或 CXCR5 ⁺，类别转换 B 细胞。其次，对于困在用那他珠单抗（抗 VLA-4 抗体n）治疗的 MS 患者血液中的CXCR3 ⁺记忆 B 细胞= 15)，潜伏的 EBV 感染对应于 GC 样条件下抗 EBNA1 IgG 分泌浆细胞的体外形成增强。这些发现意味着 B 细胞中 EBV 的持续存在增强了 MS 中的大脑归巢和抗体产生 CXCR3 ⁺子集。

更新日期：2020-11-05

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