近日,，美國哈佛大學(xué)醫(yī)學(xué)院和德國科隆大學(xué)的研究人員制作了一種B淋巴細(xì)胞可以表達EB病毒膜蛋白LMP1(latent membrane protein 1)的小鼠,，可作為淋巴瘤的動物模型,。相關(guān)論文發(fā)表在2月17日的Cell雜志上,。
EB病毒(Epstein-Barr virus,，EBV)是Epstein和Barr于1964年首次成功地將Burkitt非洲兒童淋巴瘤細(xì)胞通過體外懸浮培養(yǎng)而建株,，并在建株細(xì)胞涂片中用電鏡觀察到皰疹病毒顆粒,，故名,。由EBV感染引起或與EBV感染有關(guān)疾病主要有三種：傳染性單核細(xì)胞增多癥,、非洲兒童淋巴瘤和鼻咽癌。
EB病毒僅能在B淋巴細(xì)胞中增殖,，可使其轉(zhuǎn)化,，能長期傳代,。被病毒感染的細(xì)胞具有EB病毒的基因組，并可產(chǎn)生各種抗原,。在免疫抑制的情況下,，EB病毒可以從被感染的細(xì)胞中脫離出來，進而感染其他細(xì)胞,，引發(fā)病癥,。
研究人員發(fā)現(xiàn)，如同被EB病毒感染的人B細(xì)胞一樣,，LMP1+ B細(xì)胞將會被T細(xì)胞立即清除,。而破壞免疫監(jiān)視將導(dǎo)致快速、致命的淋巴細(xì)胞增殖和淋巴瘤的產(chǎn)生,。
研究表明,，LMP1在免疫監(jiān)視和EB病毒感染的B細(xì)胞轉(zhuǎn)化方面發(fā)揮著中心作用。這種條件性表達LMP1蛋白的小鼠模型可以用于EB病毒誘發(fā)的免疫監(jiān)視和淋巴瘤的研究,，并且可以驗證治療淋巴瘤的新方法是否有效,。（生物谷Bioon.com）
doi:10.1016/j.cell.2011.12.031
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Immune Surveillance and Therapy of Lymphomas Driven by Epstein-Barr Virus Protein LMP1 in a Mouse Model
Baochun Zhang, Sven Kracker, Tomoharu Yasuda1, Stefano Casola, Matthew Vanneman, Cornelia Hmig-Hlze, Zhe Wang, Emmanue Derudder, Shuang Li, Tirtha Chakraborty, Shane E. Cotter, Shohei Koyama, Treeve Currie, Gordon J. Freeman, Jeffery L. Kutok, Scott J. Rodig, Glenn Dranoff, Klaus Rajewsky
B cells infected by Epstein-Barr virus (EBV), a transforming virus endemic in humans, are rapidly cleared by the immune system, but some cells harboring the virus persist for life. Under conditions of immunosuppression, EBV can spread from these cells and cause life-threatening pathologies. We have generated mice expressing the transforming EBV latent membrane protein 1 (LMP1), mimicking a constitutively active CD40 coreceptor, specifically in B cells. Like human EBV-infected cells, LMP1+ B cells were efficiently eliminated by T cells, and breaking immune surveillance resulted in rapid, fatal lymphoproliferation and lymphomagenesis. The lymphoma cells expressed ligands for a natural killer (NK) cell receptor, NKG2D, and could be targeted by an NKG2D-Fc fusion protein. These experiments indicate a central role for LMP1 in the surveillance and transformation of EBV-infected B cells in vivo, establish a preclinical model for B cell lymphomagenesis in immunosuppressed patients, and validate a new therapeutic approach.
