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首页> 美国卫生研究院文献>The Journal of Experimental Medicine >Early Induction of Cyclin D2 Expression in Phorbol Ester–responsive B-1 Lymphocytes
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Early Induction of Cyclin D2 Expression in Phorbol Ester–responsive B-1 Lymphocytes

机译：Phorbol酯反应性B-1淋巴细胞中Cyclin D2表达的早期诱导

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摘要

B-1 lymphocytes represent a distinct B cell subset with characteristic features that include self-renewing capacity and unusual mitogenic responses. B-1 cells differ from conventional B cells in terms of the consequences of phorbol ester treatment: B-1 cells rapidly enter S phase in response to phorbol ester alone, whereas B-2 cells require a calcium ionophore in addition to phorbol ester to trigger cell cycle progression. To address the mechanism underlying the varied proliferative responses of B-1 and B-2 cells, we evaluated the expression and activity of the G1 cell cycle regulator, cyclin D2, and its associated cyclin-dependent kinases (Cdks). Cyclin D2 expression was upregulated rapidly, within 2–4 h, in phorbol ester–stimulated B-1 cells, in a manner dependent on intact transcription/translation, but was not increased in phorbol ester– stimulated B-2 cells. Phorbol ester–stimulated cyclin D2 expression was accompanied by the formation of cyclin D2–Cdk4, and, to a lesser extent, cyclin D2–Cdk6, complexes; cyclin D2– containing complexes were found to be catalytically functional, in terms of their ability to phosphorylate exogenous Rb in vitro and to specifically phosphorylate endogenous Rb on serine780 in vivo. These results strongly suggest that the rapid induction of cyclin D2 by a normally nonmitogenic phorbol ester stimulus is responsible for B-1 cell progression through G1 phase. The ease and rapidity with which cyclin D2 responds in B-1 cells may contribute to the proliferative features of this subset.
机译：B-1淋巴细胞代表独特的B细胞亚群，其特征包括自我更新能力和异常的促有丝分裂反应。 B-1细胞与常规B细胞在佛波酯处理的后果方面有所不同：B-1细胞仅对佛波酯有反应便迅速进入S期，而B-2细胞除佛波酯外还需要钙离子载体来触发细胞周期进程。为了解决潜在的B-1和B-2细胞增殖应答机制，我们评估了G1细胞周期调节剂cyclin D2及其相关的细胞周期蛋白依赖性激酶（Cdks）的表达和活性。在受佛波酯刺激的B-1细胞中，细胞周期蛋白D2的表达在2-4小时内迅速上调，其方式取决于完整的转录/翻译，但在受佛波酯刺激的B-2细胞中却没有增加。佛波酯刺激的细胞周期蛋白D2的表达伴随着细胞周期蛋白D2-Cdk4的形成，在较小程度上，细胞周期蛋白D2-Cdk6是复合物。发现含有细胞周期蛋白D2的复合物具有催化功能，因为它们能够在体外磷酸化外源Rb，并在体内特异性磷酸化丝氨酸 780 上的内源性Rb。这些结果强烈表明，正常的非促有丝分裂佛波酯刺激物对细胞周期蛋白D2的快速诱导是导致B-1细胞通过G1期发展的原因。细胞周期蛋白D2在B-1细胞中反应的便捷性和快速性可能有助于该亚群的增殖特征。

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