EA2216, INSERM ESPRI, ERI 29, Université de Brest and LabEx IGO, Brest, France.
EA2216, INSERM ESPRI, ERI 29, Université de Brest and LabEx IGO, Brest, France; Department of Nephrology, CHRU Cavale Blanche, Brest, France.
J Autoimmun. 2015 May;59:53-60. doi: 10.1016/j.jaut.2015.02.004. Epub 2015 Mar 7.
A number of studies have suggested that B cell mediated-regulation contributes to the establishment of immunological tolerance. However, the precise mechanisms by which regulatory B cells establish and maintain tolerance in humans remain to be determined. The objective of the current study is to understand the cellular and molecular bases of B-cell regulatory functions in humans. To describe the mechanisms regulating the functional plasticity of regulatory B cells, we used an in vitro co-culture model based on autologous mixed lymphocyte cultures involving freshly isolated B and T cells. The results show that activated B cells regulate T cell proliferation through producing transforming growth factor (TGF)-β and indoleamine 2,3-dioxygenase (IDO). The production of TGF-β and IDO leads to the induction of not only "natural" regulatory T cells but also of TGF-β-producing CD4(+) T cells and IL-10-producing regulatory T cells. Furthermore, we evidenced for the first time that CTLA-4 induces B-cells to produce IDO and to become effective induced regulatory B cells (iBregs). This study emphasizes a novel regulatory axis and open news insights in how to manage regulatory B cell functions in autoimmunity.
许多研究表明，B 细胞介导的调节有助于建立免疫耐受。然而，调节性 B 细胞在人体内建立和维持耐受的确切机制仍有待确定。本研究的目的是了解人类 B 细胞调节功能的细胞和分子基础。为了描述调节调节性 B 细胞功能可塑性的机制，我们使用了基于自体混合淋巴细胞培养的体外共培养模型，涉及新鲜分离的 B 和 T 细胞。结果表明，活化的 B 细胞通过产生转化生长因子 (TGF)-β 和吲哚胺 2,3-双加氧酶 (IDO) 来调节 T 细胞增殖。TGF-β 和 IDO 的产生不仅诱导了“天然”调节性 T 细胞，还诱导了 TGF-β 产生的 CD4(+) T 细胞和 IL-10 产生的调节性 T 细胞。此外，我们首次证明 CTLA-4 诱导 B 细胞产生 IDO 并成为有效的诱导调节性 B 细胞 (iBregs)。这项研究强调了一个新的调节轴，并为如何在自身免疫中管理调节性 B 细胞功能提供了新的见解。
