DEC1/STRA13 is a key negative regulator of activation-induced proliferation of human B cells highly expressed in anergic cells
DEC1/STRA13 is a key negative regulator of activation-induced proliferation of human B cells highly expressed in anergic cells
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DOI：
10.1016/j.imlet.2018.03.014
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发表时间：
2018-06-01
影响因子：
4.4
通讯作者：
Visentini, Marcella
中科院分区：
文献类型：
--
作者：
Camponeschi, Alessandro;Todi, Laura;Visentini, Marcella
转录因子DEC1/STRA13（也称为BHLHE40和SHARP2）参与许多过程，包括抑制细胞增殖和延迟细胞周期，并且是小鼠B细胞活化和发育的负调节因子。我们在此表明，与小鼠不同，DEC1/STRA13 表达是通过 B 细胞受体 (BCR) 或 Toll 样受体 9 (TLR9) 激活而在人类幼稚和记忆静息 B 细胞中诱导的。 DEC1/STRA13 的 siRNA 沉默增加了激活的 B 细胞在 TLR9 连接后进行大量分裂的能力。这表明 DEC1/STRA13 是激活的人类 B 细胞克隆扩增的关键负调节因子。我们还表明，DEC1/STRA13 在 HCV 相关混合冷球蛋白血症患者中克隆扩增的人类无反应 CD21(know)B 细胞中表达上调，这些细胞无法响应 BCR 或 TLR9 连接而增殖。然而，DECI/STRA13 的 siRNA 敲低无法恢复这些细胞对刺激的反应性，尽管它可能会提高增殖缺陷不太明显的无反应细胞亚群的增殖能力。
The transcription factor DEC1/STRA13 (also known as BHLHE40 and SHARP2) is involved in a number of processes including inhibition of cell proliferation and delay of cell cycle, and is a negative regulator of B cell activation and development in mice. We show here that, unlike in mice, DEC1/STRA13 expression is induced in human naive and memory resting B cells by activation through the B-cell receptor (BCR) or Toll-like receptor 9 (TLR9). siRNA silencing of DEC1/STRA13 increases the capacity of activated B cells to perform a high number of divisions after TLR9 ligation. This identifies DEC1/STRA13 as a critical negative regulator of clonal expansion of activated human B cells. We also show that DEC1/STRA13 is upregulated in human anergic CD21(know)B cells clonally expanded in patients with HCV-associated mixed cryoglobulinemia, which fail to proliferate in response to BCR or TLR9 ligation. siRNA knockdown of DECI/STRA13, however, fails to restore responsiveness to stimuli in these cells, although it might improve the proliferative capacity in a subset of anergic cells with less pronounced proliferative defect.