Klaewsongkram Jettanong, Yang Yinhua, Golech Susanne, Katz Jonathan, Kaestner Klaus H, Weng Nan-Ping
Laboratory of Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
J Immunol. 2007 Oct 1;179(7):4679-84. doi: 10.4049/jimmunol.179.7.4679.
Krüppel-like factor 4 (Klf4) is a transcription factor and functions in regulating cell differentiation, cell growth, and cell cycle. Although Klf4 is expressed in lymphocytes, its function in lymphocytes is unknown. In this study, we report that the levels of Klf4 expression were low in pro-B cells and continuously increased in pre-B and in mature B cells. Upon activation, Klf4 was rapidly decreased in mature B cells after 2 h of activation. A modest decrease in numbers of pre-B cells in bone marrow and mature B cells in spleen was observed in Klf4-deficient mice. In the absence of Klf4, fewer B cells entered the S phase of the cell cycle and completed cell division in response to the engagement of BCR and/or CD40 in vitro. Furthermore, the delay in entering the cell cycle is associated with decreased expression of cyclin D2 in B cells that lack Klf4 expression. We then demonstrated that Klf4 directly bound to the promoter of cyclin D2 and regulated its expression. These findings demonstrate that Klf4 regulates B cell number and activation-induced B cell proliferation through directly acting on the promoter of cyclin D2.
Krüppel样因子4（Klf4）是一种转录因子，在调节细胞分化、细胞生长和细胞周期中发挥作用。尽管Klf4在淋巴细胞中表达，但其在淋巴细胞中的功能尚不清楚。在本研究中，我们报道Klf4在pro-B细胞中的表达水平较低，而在pre-B细胞和成熟B细胞中持续升高。激活后，成熟B细胞在激活2小时后Klf4迅速下降。在Klf4缺陷小鼠中，观察到骨髓中的pre-B细胞和脾脏中的成熟B细胞数量适度减少。在缺乏Klf4的情况下，较少的B细胞进入细胞周期的S期，并在体外响应BCR和/或CD40的结合完成细胞分裂。此外，进入细胞周期的延迟与缺乏Klf4表达的B细胞中细胞周期蛋白D2的表达降低有关。然后我们证明Klf4直接结合细胞周期蛋白D2的启动子并调节其表达。这些发现表明，Klf4通过直接作用于细胞周期蛋白D2的启动子来调节B细胞数量和激活诱导的B细胞增殖。
