Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, USA.
Blood. 2011 Oct 13;118(15):4174-8. doi: 10.1182/blood-2011-01-331181. Epub 2011 Aug 19.
Initial cell surface expression of the pre-B cell receptor induces proliferation. After 2 to 5 divisions, however, large pre-BII (Fraction C') cells exit cell cycle to become resting, small pre-BII cells (Fraction D). The mechanism by which pre-BII cells exit cell cycle, however, is currently unclear. The checkpoint at the Fraction C'-D transition is critical for immunoglobulin light chain gene recombination and to prevent malignant transformation into acute lymphoblastic leukemia. Here we demonstrate that inducible activation of pre-B cell receptor signaling induces cell-cycle exit through up-regulation of the transcriptional repressor BCL6. Inducible activation of BCL6 downstream of the pre-B cell receptor results in transcriptional repression of MYC and CCND2. Hence, pre-B cell receptor-mediated activation of BCL6 limits pre-B cell proliferation and induces cellular quiescence at the small pre-BII (Fraction D) stage.
初始前 B 细胞受体的表面表达可诱导细胞增殖。然而，在 2 到 5 次分裂后，大量前 BII（C' 亚群）细胞退出细胞周期，成为静止的小前 BII 细胞（D 亚群）。然而，前 BII 细胞退出细胞周期的机制目前尚不清楚。C' 亚群到 D 亚群的转变检查点对于免疫球蛋白轻链基因重排和防止恶性转化为急性淋巴细胞白血病至关重要。在这里，我们证明了前 B 细胞受体信号的诱导激活通过上调转录抑制因子 BCL6 诱导细胞周期退出。在前 B 细胞受体下游诱导 BCL6 的激活会导致 MYC 和 CCND2 的转录抑制。因此，前 B 细胞受体介导的 BCL6 激活限制了前 B 细胞的增殖，并在前 BII（D 亚群）阶段诱导细胞静止。
