Department for Medical Microbiology and Hygiene, Interfacultary Institute for Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
Front Immunol. 2020 Jan 24;10:3093. doi: 10.3389/fimmu.2019.03093. eCollection 2019.
B cells fulfill multifaceted functions that influence immune responses during health and disease. In autoimmune diseases, such as inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, depletion of functional B cells results in an aggravation of disease in humans and respective mouse models. This could be due to a lack of a pivotal B cell subpopulation: regulatory B cells (Bregs). Although Bregs represent only a small proportion of all immune cells, they exhibit critical properties in regulating immune responses, thus contributing to the maintenance of immune homeostasis in healthy individuals. In this study, we report that the induction of Bregs is differentially triggered by the immunogenicity of the host microbiota. In comparative experiments with low immunogenic and strong immunogenic , we found that the induction and longevity of Bregs depend on strong Toll-like receptor activation mediated by antigens of strong immunogenic commensals. The potent B cell stimulation via led to a pronounced expression of suppressive molecules on the B cell surface and an increased production of anti-inflammatory cytokines like interleukin-10. These bacteria-primed Bregs were capable of efficiently inhibiting the maturation and function of dendritic cells (DCs), preventing the proliferation and polarization of T helper (Th)1 and Th17 cells while simultaneously promoting Th2 cell differentiation . In addition, Bregs facilitated the development of regulatory T cells (Tregs) resulting in a possible feedback cooperation to establish immune homeostasis. Moreover, the colonization of germfree wild type mice with but not significantly reduced intestinal inflammatory processes in dextran sulfate sodium (DSS)-induced colitis associated with an increase induction of immune suppressive Bregs. The quantity of Bregs directly correlated with the severity of inflammation. These findings may provide new insights and therapeutic approaches for B cell-controlled treatments of microbiota-driven autoimmune disease.
B 细胞具有多种功能，可影响健康和疾病期间的免疫反应。在自身免疫性疾病（如炎症性肠病、多发性硬化症和类风湿性关节炎）中，功能性 B 细胞的耗竭会导致人类和相应的小鼠模型中疾病加重。这可能是由于缺乏关键的 B 细胞亚群：调节性 B 细胞（Bregs）。尽管 Bregs 仅占所有免疫细胞的一小部分，但它们在调节免疫反应方面具有关键特性，有助于维持健康个体的免疫稳态。在这项研究中，我们报告称，宿主微生物群的免疫原性可差异地触发 Bregs 的诱导。在低免疫原性和强免疫原性的比较实验中，我们发现 Bregs 的诱导和寿命取决于强免疫原性共生菌抗原介导的强烈 Toll 样受体激活。通过 强烈刺激 B 细胞会导致 B 细胞表面抑制性分子的显著表达，并增加抗炎细胞因子如白细胞介素-10 的产生。这些经细菌激活的 Bregs 能够有效地抑制树突状细胞（DC）的成熟和功能，防止 T 辅助（Th）1 和 Th17 细胞的增殖和极化，同时促进 Th2 细胞分化。此外，Bregs 促进了调节性 T 细胞（Tregs）的发育，从而可能形成反馈合作以建立免疫稳态。此外，用 定植无菌野生型小鼠，但不用 定植，可显著减轻葡聚糖硫酸钠（DSS）诱导的结肠炎相关的肠道炎症过程，同时增加免疫抑制性 Bregs 的诱导。Bregs 的数量与炎症的严重程度直接相关。这些发现可能为基于 B 细胞控制的微生物群驱动的自身免疫性疾病治疗提供新的见解和治疗方法。
