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首页> 外文期刊>The journal of immunology >Transcription Factor ABF-1 Suppresses Plasma Cell Differentiation but Facilitates Memory B Cell Formation
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Transcription Factor ABF-1 Suppresses Plasma Cell Differentiation but Facilitates Memory B Cell Formation

机译:转录因子ABF-1抑制浆细胞分化,但有助于记忆B细胞形成

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Ag-primed B cells that result from an immune response can form either memory B cells or Ab-secreting plasma cells; however, the molecular machinery that controls this cellular fate is poorly understood. In this study, we show that activated B cell factor-1 (ABF-1), which encodes a basic helix-loop-helix transcriptional repressor, participates in this regulation. ABF-1 was prevalently expressed in purified memory B cells and induced by T follicular helper cell–mediated signals. ABF-1 expression declined by the direct repression of B lymphocyte–induced maturation protein-1 during differentiation. Ectopic expression of ABF-1 reduced the formation of Ab-secreting cells in an in vitro differentiation system of human memory B cells. Accordingly, knockdown of ABF-1 potentiates the formation of Ab-secreting cells. A transgenic mouse that expresses inducible ABF-1 in a B cell–specific manner was generated to demonstrate that the formation of germinal center and memory B cells was augmented by induced ABF-1 in an immune response, whereas the Ag-specific plasma cell response was dampened. This effect was associated with the ability of ABF-1 to limit cell proliferation. Together, our results demonstrate that ABF-1 facilitates formation of memory B cells but prevents plasma cell differentiation.
机译:免疫应答产生的由Ag引发的B细胞可以形成记忆B细胞或分泌Ab的浆细胞。然而,人们对控制这种细胞命运的分子机制知之甚少。在这项研究中,我们表明,激活的B细胞因子1(ABF-1)编码此基本的螺旋-环-螺旋转录阻遏物,参与此调节。 ABF-1在纯化的记忆B细胞中普遍表达,并由T滤泡辅助细胞介导的信号诱导。在分化过程中,B淋巴细胞诱导的成熟蛋白1的直接阻遏使ABF-1的表达下降。 ABF-1的异位表达减少了人类记忆B细胞体外分化系统中分泌Ab的细胞的形成。因此,敲除ABF-1可增强Ab分泌细胞的形成。产生了以B细胞特异性方式表达可诱导ABF-1的转基因小鼠,以证明在免疫应答中诱导的ABF-1可以促进生发中心和记忆B细胞的形成,而Ag特异性浆细胞应答被弄湿了。该作用与ABF-1限制细胞增殖的能力有关。在一起,我们的结果表明ABF-1促进记忆B细胞的形成,但阻止浆细胞分化。

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