澳大利亞沃爾特-伊萊扎·霍爾醫(yī)學(xué)研究所科學(xué)家近日的一項(xiàng)新發(fā)現(xiàn)，將改變?nèi)藗冮L期以來對(duì)身體免疫系統(tǒng)記憶能力運(yùn)作機(jī)制的看法,。研究結(jié)果發(fā)表在了《科學(xué)》雜志上,。
記憶B細(xì)胞作為免疫細(xì)胞的一種,，在長期記憶中起著至關(guān)重要的作用。“對(duì)現(xiàn)階段所有正在使用的疫苗的有效性來說,，B細(xì)胞以及相應(yīng)抗體的生產(chǎn)是關(guān)鍵的一步”,，參與研究的David Tarlinton表示，“因此進(jìn)一步研究并清晰地認(rèn)識(shí)免疫過程中的分子相互作用原理,，是很重要的”,。
在這項(xiàng)實(shí)驗(yàn)中，Tarlinton和其同事Ingela Vikstrom博士對(duì)一種被稱為“促存活”蛋白進(jìn)行研究,，這種蛋白能夠控制記憶B細(xì)胞的存活,。Vikstrom博士表示，B細(xì)胞的記憶在一種被稱為“生發(fā)中心”的臨時(shí)細(xì)胞結(jié)構(gòu)形成,，這種細(xì)胞結(jié)構(gòu)能夠?qū)γ庖呦到y(tǒng)的活動(dòng)產(chǎn)生應(yīng)答,。
科學(xué)家們使用遺傳和藥理學(xué)手段對(duì)兩種已知的促存活蛋白Bcl-xL和Mcl-1進(jìn)行研究，驚奇地發(fā)現(xiàn)Mcl-1蛋白很大程度地影響著B細(xì)胞記憶的產(chǎn)生和保持,，而這與科學(xué)家們普遍認(rèn)為的Bcl-xL才是影響記憶B細(xì)胞關(guān)鍵蛋白的看法完全不同,。
Mcl-1蛋白對(duì)癌細(xì)胞來說，是一種重要的存活蛋白,。這一發(fā)現(xiàn)可能會(huì)讓人們對(duì)癌癥治療產(chǎn)生新認(rèn)識(shí),，同時(shí)，這一發(fā)現(xiàn)也將對(duì)自身免疫性疾病治療和抑制移植排斥反應(yīng)的研究產(chǎn)生影響,。（生物谷Bioon.com）
生物谷推薦英文摘要：
Science DOI: 10.1126/science.1191793
Mcl-1 is Essential for Germinal Center Formation and B Cell Memory
Ingela Vikstrom,1 Sebastian Carotta,1 Katja Lüthje,1 Victor Peperzak,1 Philipp J. Jost,1 Stefan Glaser,1 Meinrad Busslinger,2 Philippe Bouillet,1,3 Andreas Strasser,1,3 Stephen L. Nutt,1,3 David M. Tarlinton1,3,*
Lymphocyte survival during immune responses is controlled by the relative expression of pro- and anti-apoptotic molecules, regulating the magnitude, quality, and duration of the response. Here, we investigate the consequences of deleting genes encoding the anti-apoptotic molecules Mcl1 and Bcl2l1 (Bcl-xL) from B cells using an inducible system synchronized with expression of activation-induced cytidine deaminase (Aicda) following immunization. This revealed Mcl1 and not Bcl2l1 to be indispensable for formation and persistence of germinal centers (GC). Limiting Mcl1 expression reduced the magnitude of the GC response with an equivalent, but not greater, effect on memory B cell formation and no effect on persistence. Our results identify Mcl1 as the main anti-apoptotic regulator of activated B cell survival and suggest distinct mechanisms controlling survival of GC and memory B cells.
1 Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
2 Research Institute of Molecular Pathology, Vienna Biocenter, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.
3 Department of Medical Biology, University of Melbourne, Parkville, Victoria 3050, Australia.
