Institute of Neuropathology, University Medical Centre Göttingen, Göttingen, Germany.
Fraunhofer-Institute for Translational Medicine and Pharmacology ITMP, Göttingen, Germany.
Acta Neuropathol. 2023 Apr;145(4):461-477. doi: 10.1007/s00401-023-02552-6. Epub 2023 Mar 1.
B cells contribute to chronic inflammatory conditions as source of antibody-secreting plasma cells and as antigen-presenting cells activating T cells, making anti-CD20-mediated B cell depletion a widely used therapeutic option. B cells or B cell subsets may, however, exert regulatory effects, while to date, the immunological and/or clinical impact of these observations remained unclear. We found that in multiple sclerosis (MS) patients, B cells contain regulatory features and that their removal enhanced activity of monocytes. Using a co-culture system, we identified B cell-provided interleukin (IL)-10 as key factor in controlling pro-inflammatory activity of peripheral myeloid cells as well as microglia. Depleting B cells via anti-CD20 in a mouse model of MS unleashed the activity of myeloid cells and microglia and accelerated disease severity; in contrast, adoptive transfer of IL-10-providing B cells restored in vivo control of central nervous system (CNS) macrophages and microglia and reversed clinical exacerbation. These findings suggest that B cells exert meaningful regulatory properties, which should be considered when designing novel B cell-directed agents.
B 细胞作为产生抗体分泌浆细胞和抗原呈递细胞激活 T 细胞的来源，参与慢性炎症状态，因此抗 CD20 介导的 B 细胞耗竭成为广泛应用的治疗选择。然而，B 细胞或 B 细胞亚群可能发挥调节作用，而这些观察结果的免疫和/或临床影响迄今为止仍不清楚。我们发现，在多发性硬化症（MS）患者中，B 细胞具有调节功能，去除 B 细胞可增强单核细胞的活性。我们使用共培养系统发现，B 细胞提供的白细胞介素（IL）-10 是控制外周髓样细胞和小胶质细胞促炎活性的关键因素。在 MS 的小鼠模型中通过抗 CD20 耗竭 B 细胞会释放髓样细胞和小胶质细胞的活性，加速疾病严重程度；相比之下，过继转移提供 IL-10 的 B 细胞可恢复中枢神经系统（CNS）巨噬细胞和小胶质细胞的体内控制，并逆转临床恶化。这些发现表明 B 细胞具有有意义的调节特性，在设计新型 B 细胞靶向药物时应予以考虑。
