Gu Zhimin, Zhou Wen, Huang Junwei, Yang Ye, Wendlandt Erik, Xu Hongwei, He Xiao, Tricot Guido, Zhan Fenghuang
Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA.
Department of Internal Medicine, University of Iowa City, Carver College of Medicine, Iowa City, IA 52242, USA ; Institute of Cancer Research, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Biomed Res Int. 2014;2014:621082. doi: 10.1155/2014/621082. Epub 2014 Nov 17.
The serine/threonine kinase Nek2 is commonly found upregulated in a wide variety of neoplasms including diffuse large B cell lymphoma and multiple myeloma. High expression of Nek2 is implicated in the induction of chromosomal instability, promotion of cell proliferation, and drug resistance in tumor cells as well as a marker for poor clinical outcomes. Despite its well recorded involvement in chromosomal instability and neoplastic growth, little is known about the involvement of Nek2 in B cell development. Here we report the development of a transgenic mouse line with conditional expression of Nek2 in the B cell lineage and the effects it has on the development of B cells. Interestingly, we found that the overexpression of Nek2 does not induce spontaneous tumor formation within the transgenic mice up to 24 months after induction. Instead, overexpression of Nek2 in the B cell lineage affects the development of B cells by increasing the proportion of immature B cells in the bone marrow and decreasing B-1 B cells in peritoneal cavity. Furthermore, Nek2 transgenic mice develop spontaneous germinal centers and exhibit an enhanced T cell dependent immune response. Altogether, our data demonstrates a novel role for Nek2 in regulating B cell development and the immune response.
丝氨酸/苏氨酸激酶Nek2在包括弥漫性大B细胞淋巴瘤和多发性骨髓瘤在内的多种肿瘤中通常上调。Nek2的高表达与肿瘤细胞中染色体不稳定性的诱导、细胞增殖的促进、耐药性以及不良临床结果的标志物有关。尽管其在染色体不稳定性和肿瘤生长中的作用已有充分记录，但关于Nek2在B细胞发育中的作用知之甚少。在此，我们报告了一种在B细胞谱系中条件性表达Nek2的转基因小鼠品系的建立及其对B细胞发育的影响。有趣的是，我们发现Nek2的过表达在诱导后长达24个月的转基因小鼠中不会诱导自发肿瘤形成。相反，B细胞谱系中Nek2的过表达通过增加骨髓中未成熟B细胞的比例和减少腹腔中B-1 B细胞来影响B细胞的发育。此外，Nek2转基因小鼠会自发形成生发中心，并表现出增强的T细胞依赖性免疫反应。总之，我们的数据证明了Nek2在调节B细胞发育和免疫反应中的新作用。
