Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University and Center for Cognitive Neuroscience, 5020 Salzburg, Austria.
Clinical Division of Social Psychiatry, Department of Psychiatry and Psychotherapy, Medical University of Vienna, 1090 Vienna, Austria.
Cells. 2022 Aug 25;11(17):2649. doi: 10.3390/cells11172649.
The chemokine C-X-C- ligand 13 (CXCL13) is a major B cell chemoattractant to B cell follicles in secondary lymphoid organs (SLO) that proposedly recruits B cells to the cerebrospinal fluid (CSF) during neuroinflammation. CXCR5, the cognate receptor of CXCL13, is expressed on B cells and certain T cell subsets, in particular T follicular helper cells (Tfh cells), enabling them to follow CXCL13 gradients towards B cell follicles for spatial proximity, a prerequisite for productive T cell-B cell interaction. Tfh cells are essential contributors to B cell proliferation, differentiation, and high-affinity antibody synthesis and are required for germinal center formation and maintenance. Circulating Tfh cells (cTfh) have been observed in the peripheral blood and CSF. Furthermore, CXCL13/CXCR5-associated immune activities organize and shape adaptive B cell-related immune responses outside of SLO via the formation of ectopic lymphoid structures in inflamed tissues, including the central nervous system (CNS). This review summarizes the recent advances in our understanding of the CXCL13/CXCR5 immune axis and its role in vaccination, autoimmunity, and infection with a special focus on its relevance for intrathecal B cell activities in inflammatory CNS diseases.
趋化因子 C-X-C-配体 13（CXCL13）是次级淋巴器官（SLO）中 B 细胞滤泡的主要趋化因子，据称它在神经炎症期间将 B 细胞募集到脑脊液（CSF）中。CXCL13 的同源受体 CXCR5 表达在 B 细胞和某些 T 细胞亚群上，特别是滤泡辅助 T 细胞（Tfh 细胞）上，使它们能够跟随 CXCL13 梯度向 B 细胞滤泡移动，以实现空间接近，这是 T 细胞-B 细胞相互作用产生的前提。Tfh 细胞是 B 细胞增殖、分化和高亲和力抗体合成的重要贡献者，是生发中心形成和维持所必需的。循环滤泡辅助 T 细胞（cTfh）已在外周血和 CSF 中观察到。此外，CXCL13/CXCR5 相关的免疫活动通过在炎症组织中形成异位淋巴样结构，包括中枢神经系统（CNS），在外周淋巴器官之外组织和塑造适应性 B 细胞相关免疫反应。本综述总结了我们对 CXCL13/CXCR5 免疫轴及其在疫苗接种、自身免疫和感染中的作用的最新认识，特别关注其与炎症性中枢神经系统疾病中鞘内 B 细胞活性的相关性。
