The influence of signals perceived by immature B cells during their development in bone marrow on their subsequent functions as mature cells are poorly defined. Here, we show that bone marrow cells transiently stimulated in vivo or in vitro through the Toll-like receptor 9 generate proB cells (CpG-proBs) that interrupt experimental autoimmune encephalomyelitis (EAE) when transferred at the onset of clinical symptoms. Protection requires differentiation of CpG-proBs into mature B cells that home to reactive lymph nodes, where they trap T cells by releasing the CCR7 ligand, CCL19, and to inflamed central nervous system, where they locally limit immunopathogenesis through interleukin-10 production, thereby cooperatively inhibiting ongoing EAE. These data demonstrate that a transient inflammation at the environment, where proB cells develop, is sufficient to confer regulatory functions onto their mature B-cell progeny. In addition, these properties of CpG-proBs open interesting perspectives for cell therapy of autoimmune diseases.

中文翻译：

---

用活化的B细胞祖细胞治疗成熟的自身免疫性脑脊髓炎，使其成熟后进入调节性B细胞。

未成熟的B细胞在骨髓发育过程中感知到的信号对其作为成熟细胞的后续功能的影响定义不清。在这里，我们显示在体内或体外通过Toll样受体9短暂刺激的骨髓细胞产生proB细胞（CpG-proBs），当临床症状发作时，该proB细胞会中断实验性自身免疫性脑脊髓炎（EAE）。保护需要将CpG-proBs分化成成熟的B​​细胞，该B细胞驻留在反应性淋巴结中，在那里它们通过释放CCR7配体CCL19捕获T细胞，并发炎的中枢神经系统，在那里它们通过白介素10的产生局部限制免疫发病机制，从而合作抑制正在进行的EAE。这些数据表明，proB细胞在环境中短暂发炎，足以赋予其成熟的B细胞后代以调节功能。此外，CpG-proBs的这些特性为自身免疫性疾病的细胞治疗开辟了有趣的前景。