Blood：关键蛋白可保证免疫细胞发挥正常功能

近日，来自国外的研究人员研究发现，机体许多抵御感染的免疫细胞需要一种细胞存活蛋白A1来使得细胞发育和维持正常功能。研究者的发现将对于我们更好地理解白血病、过敏症以及自体免疫疾病提供了一定的线索。研究者发现淋巴细胞和粒细胞如果没有蛋白质A1，则不能发育或者不能对感染产生效应。

蛋白质A1是Bcl-2蛋白质家族的一员，可以控制细胞的生存。研究者从免疫细胞中剔除A1蛋白，然后研究缺少A1后免疫细胞的功能以及其发育状况，相关研究成果刊登在了国际著名杂志Blood上。研究者Herold博士表示，10多年以来，我们已经知道了细胞生存的蛋白质，如Bcl-2对于免疫细胞的发育和功能都非常重要，因为A1蛋白质一般不会和其它蛋白质一块合作发挥作用，所以研究者都忽略了该蛋白质，目前研究者的工作揭示了A1在免疫系统功能的正常发挥扮演了很多重要的角色。

研究者表示这项研究将为我们认识很多人类疾病提供了帮助，比如很多疾病，白血病、自体免疫疾病等都是因为机体存在功能不全的免疫细胞引起的。这项研究揭示了蛋白质A1对于免疫细胞的功能发挥必不可少，同时研究者也给予了我们提出A1蛋白质的工具方法，目前研究者正在深入研究是否细胞中蛋白质A1的存在对于白血病、过敏症和自体免疫疾病必不可少，如果确实如此，A1将成为这些疾病治疗的一个新的靶点。（生物谷Bioon.com）

编译自：Survival factor for immune cells located

编译者：T.Shen

doi:10.1182/blood-2011-12-399089
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Targeting anti-apoptotic A1/Bfl-1 by in vivo RNAi reveals multiple roles in leukocyte development in mice

Eleonora Ottina1, Francesca Grespi1, Denise Tischner1, Claudia Soratroi1, Stephan Geley2, Andreas Ploner3, Holger M. Reichardt4, Andreas Villunger1,*, and Marco J. Herold5

Gene-targeting studies in mice have identified the essential roles of most pro-survival Bcl-2 family members in normal physiology and under conditions of stress. The function of one member, Bcl2a1/Bfl-1/A1, is only poorly understood due to quadruplication of the gene locus in mice, hindering conventional knockout studies. To overcome this problem, we generated mouse models allowing traceable constitutive or reversible ablation of A1 in the hematopoietic system by RNA interference. Knockdown of A1 impaired early stages of T cell differentiation, B cell homeostasis and sensitized transitional as well as follicular B cells to apoptosis induced by ligation of the B cell receptor. As a consequence B cell proliferation in response to mitogens was severely impaired while that of T cells appeared unaffected. Furthermore, depending on the extent of A1 knockdown, granulocytes showed increased spontaneous death in culture or failed to accumulate in significant numbers in vivo. These models highlight the critical role of A1 in leukocyte development and homeostasis, constituting valuable tools for investigating presumed roles of this Bcl-2 family member in immunity, tumorigenesis and drug-resistance.