Class-switch recombination (CSR) is essential for humoral immunity. However, the regulation of CSR is not completely understood. Here we demonstrate that phosphatidylinositol 3-kinase (PI3K) actively suppressed the onset and frequency of CSR in primary B cells. Consistently, mice lacking the lipid phosphatase, PTEN, in B cells exhibited a hyper-IgM condition due to impaired CSR, which could be restored in vitro by specific inhibition of PI3Kdelta. Inhibition of CSR by PI3K was partially dependent on the transcription factor, BLIMP1, linking plasma cell commitment and cessation of CSR. PI3K-dependent activation of the serine-threonine kinase, Akt, suppressed CSR, in part, through the inactivation of the Forkhead Box family (Foxo) of transcription factors. Reduced PI3K signaling enhanced the expression of AID (activation-induced cytidine deaminase) and accelerated CSR. However, ectopic expression of AID could not fully overcome inhibition of CSR by PI3K, suggesting that PI3K regulates both the expression and function of AID.

译文

:Class-switch recombination(CSR)对于体液免疫至关重要。但是,关于企业社会责任的规定尚不完全清楚。在这里,我们证明磷脂酰肌醇3-激酶(PI3K)积极抑制原代B细胞中CSR的发生和频率。一致地,由于CSR受损,在B细胞中缺乏脂质磷酸酶PTEN的小鼠表现出高IgM病状,可以通过特异性抑制PI3Kdelta使其在体外恢复。 PI3K对CSR的抑制部分取决于转录因子BLIMP1,这与浆细胞的定型和CSR的终止有关。丝氨酸-苏氨酸激酶Akt的PI3K依赖性激活部分地通过使转录因子的Forkhead Box家族(Foxo)失活而抑制了CSR。减少的PI3K信号传导增强了AID(激活诱导的胞苷脱氨酶)的表达并加速了CSR。然而,AID的异位表达不能完全克服PI3K对CSR的抑制作用,这表明PI3K既可以调节AID的表达又可以调节AID的功能。

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