Webb Louise M C, Datta Preeta, Bell Sarah E, Kitamura Daisuke, Turner Martin, Butcher Geoffrey W
Laboratory of Lymphocyte Signalling and Development, Babraham Institute, Cambridge CB22 3AT, United Kingdom; and.
Research Institute for Biomedical Sciences, Tokyo University of Science, Yamazaki 2669, Noda, Chiba 278-0022, Japan.
J Immunol. 2016 Jan 1;196(1):207-16. doi: 10.4049/jimmunol.1501582. Epub 2015 Nov 30.
An effective immune system depends upon regulation of lymphocyte function and homeostasis. In recent years, members of the GTPases of the immunity associated protein (GIMAP) family were proposed to regulate T cell homeostasis. In contrast, little is known about their function and mode of action in B cells. We used a combination of transgenic mice and in vivo and in vitro techniques to conditionally and electively ablate GIMAP1 in resting and activated peripheral B cells. Our data suggest that GIMAP1 is absolutely essential for the survival of peripheral B cells, irrespective of their activation state. Together with recent data showing increased expression of GIMAP1 in B cell lymphomas, our work points to the possible potential of GIMAP1 as a target for manipulation in a variety of B cell-mediated diseases.
有效的免疫系统依赖于淋巴细胞功能的调节和内环境稳定。近年来,有人提出免疫相关蛋白(GIMAP)家族的GTP酶成员可调节T细胞内环境稳定。相比之下,它们在B细胞中的功能和作用方式却鲜为人知。我们结合使用转基因小鼠以及体内和体外技术,有条件地、选择性地在静止和活化的外周B细胞中敲除GIMAP1。我们的数据表明,无论外周B细胞的激活状态如何,GIMAP1对于其存活绝对至关重要。连同最近显示GIMAP1在B细胞淋巴瘤中表达增加的数据,我们的工作指出了GIMAP1作为多种B细胞介导疾病中操纵靶点的潜在可能性。