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 Bacteroides vulgatus and strong immunogenic Escherichia coli, 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 E. coli 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 vitro. 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 E. coli but not B. vulgatus 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.

中文翻译：

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细菌免疫原性对于抑制调节性B细胞抑制炎症性免疫反应至关重要。

B细胞完成影响健康和疾病期间免疫反应的多方面功能。在诸如炎症性肠病，多发性硬化症和类风湿性关节炎的自身免疫疾病中，功能性B细胞的耗竭导致人和相应小鼠模型中疾病的恶化。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中显示出关键特性，因此有助于维持健康个体的免疫稳态。在这项研究中，我们报告了Bregs的诱导是由宿主微生物群的免疫原性差异触发的。在具有低免疫原性拟杆菌和强免疫原性大肠杆菌的对比实验中，我们发现Bregs的诱导和寿命取决于强免疫原性抗原介导的强Toll样受体活化。通过大肠杆菌对B细胞的强力刺激导致B细胞表面抑制分子的显着表达以及抗炎细胞因子（如白介素10）的产生增加。这些由细菌引发的Bregs能够有效抑制树突状细胞（DC）的成熟和功能，防止T辅助（Th）1和Th17细胞的增殖和极化，同时在体外促进Th2细胞分化。此外，Bregs促进了调节性T细胞（Tregs）的发展，导致可能建立反馈反馈以建立免疫稳态。此外，用大肠杆菌而不是B来定殖无菌野生型小鼠。在硫酸葡聚糖硫酸钠（DSS）诱导的结肠炎中，寻常性黄体素显着减少了与增加免疫抑制性Bregs的诱导有关的肠炎。Bregs的数量与炎症的严重程度直接相关。这些发现可能为微生物群驱动的自身免疫性疾病的B细胞控制治疗提供新的见识和治疗方法。