CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation
CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation
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DOI：
10.1126/scitranslmed.3005407
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发表时间：
2013-02-20
影响因子：
17.1
通讯作者：
Mauri, Claudia
中科院分区：
文献类型：
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作者：
Flores-Borja, Fabian;Bosma, Anneleen;Mauri, Claudia
调节性B细胞在健康个体或免疫疾病患者中维持耐受性的相关性仍然研究不足。在健康个体中，CD 19（+）CD 24（hi）CD 38（hi）B细胞抑制CD 4（+）CD 25（-）T细胞增殖以及这些细胞释放干扰素-γ和肿瘤坏死因子-α;这种抑制部分通过产生白细胞介素-10（IL-10）介导。我们进一步阐明了CD 19（+）CD 24（hi）CD 38（hi）B细胞的抑制机制。健康的CD 19（+）CD 24（hi）CD 38（hi）B细胞抑制初始T细胞分化为T辅助1（T（H）1）和T（H）17细胞，并将CD 4（+）CD 25（-）T细胞转化为调节性T细胞（T-T），部分是通过产生IL-10。相反，类风湿性关节炎（RA）患者的CD 19（+）CD 24（hi）CD 38（hi）B细胞不能将CD 4（+）CD 25（-）T细胞转化为功能抑制性T细胞或抑制T（H）17的发育;然而，它们保持了抑制T（H）1细胞分化的能力。此外，与非活动性疾病患者或健康个体相比，活动性疾病RA患者外周血中CD 19（+）CD 24（hi）CD 38（hi）B细胞数量减少。这些结果表明，在活动性RA患者中，具有调节功能的CD 19（+）CD 24（hi）CD 38（hi）B细胞可能无法阻止自身反应性反应和炎症的发展，导致自身免疫。
The relevance of regulatory B cells in the maintenance of tolerance in healthy individuals or in patients with immune disorders remains understudied. In healthy individuals, CD19(+)CD24(hi)CD38(hi) B cells suppress CD4(+)CD25(-) T cell proliferation as well as the release of interferon-gamma and tumor necrosis factor-alpha by these cells; this suppression is partially mediated through the production of interleukin-10 (IL-10). We further elucidate the mechanisms of suppression by CD19(+)CD24(hi)CD38(hi) B cells. Healthy CD19(+)CD24(hi)CD38(hi) B cells inhibited naive T cell differentiation into T helper 1 (T(H)1) and T(H)17 cells and converted CD4(+)CD25(-) T cells into regulatory T cells (T-regs), in part through the production of IL-10. In contrast, CD19(+)CD24(hi)CD38(hi) B cells from patients with rheumatoid arthritis (RA) failed to convert CD4(+)CD25(-) T cells into functionally suppressive T-regs or to curb T(H)17 development; however, they maintained the capacity to inhibit T(H)1 cell differentiation. Moreover, RA patients with active disease have reduced numbers of CD19(+)CD24(hi)CD38(hi) B cells in peripheral blood compared with either patients with inactive disease or healthy individuals. These results suggest that in patients with active RA, CD19(+)CD24(hi)CD38(hi) B cells with regulatory function may fail to prevent the development of autoreactive responses and inflammation, leading to autoimmunity.