Wang Angela, Rojas Olga, Lee Dennis, Gommerman Jennifer L
Department of Immunology, University of Toronto, Toronto, ON, Canada.
Immunol Rev. 2021 Jan;299(1):45-60. doi: 10.1111/imr.12929. Epub 2020 Oct 27.
The remarkable success of anti-CD20 B cell depletion therapies in reducing the burden of multiple sclerosis (MS) disease has prompted significant interest in how B cells contribute to neuroinflammation. Most focus has been on identifying pathogenic CD20 B cells. However, an increasing number of studies have also identified regulatory functions of B lineage cells, particularly the production of IL-10, as being associated with disease remission in anti-CD20-treated MS patients. Moreover, IL-10-producing B cells have been linked to the attenuation of inflammation in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. In addition to IL-10-producing B cells, antibody-producing plasma cells (PCs) have also been implicated in suppressing neuroinflammation. This review will examine regulatory roles for B cells and PCs in MS and EAE. In addition, we speculate on the involvement of regulatory PCs and the cytokine BAFF in the context of anti-CD20 treatment. Lastly, we explore how the microbiota could influence anti-inflammatory B cell behavior. A better understanding of the contributions of different B cell subsets to the regulation of neuroinflammation, and factors that impact the development, maintenance, and migration of such subsets, will be important for rationalizing next-generation B cell-directed therapies for the treatment of MS.
抗CD20 B细胞清除疗法在减轻多发性硬化症（MS）疾病负担方面取得的显著成功，引发了人们对B细胞如何促成神经炎症的浓厚兴趣。大多数研究集中在识别致病性CD20 B细胞。然而，越来越多的研究也发现B淋巴细胞系细胞的调节功能，特别是白细胞介素-10（IL-10）的产生，与接受抗CD20治疗的MS患者的疾病缓解有关。此外，产生IL-10的B细胞与实验性自身免疫性脑脊髓炎（EAE，MS的动物模型）炎症的减轻有关。除了产生IL-10的B细胞外，产生抗体的浆细胞（PC）也被认为与抑制神经炎症有关。本综述将探讨B细胞和PC在MS和EAE中的调节作用。此外，我们推测在抗CD20治疗背景下调节性PC和细胞因子B淋巴细胞刺激因子（BAFF）的参与情况。最后，我们探讨微生物群如何影响抗炎性B细胞行为。更好地理解不同B细胞亚群对神经炎症调节的贡献，以及影响这些亚群发育、维持和迁移的因素，对于合理化用于治疗MS的下一代B细胞定向疗法至关重要。
