近日，美国哈佛大学医学院和德国科隆大学的研究人员制作了一种B淋巴细胞可以表达EB病毒膜蛋白LMP1(latent membrane protein 1)的小鼠，可作为淋巴瘤的动物模型。相关论文发表在2月17日的Cell杂志上。
EB病毒(Epstein-Barr virus，EBV)是Epstein和Barr于1964年首次成功地将Burkitt非洲儿童淋巴瘤细胞通过体外悬浮培养而建株，并在建株细胞涂片中用电镜观察到疱疹病毒颗粒，故名。由EBV感染引起或与EBV感染有关疾病主要有三种：传染性单核细胞增多症、非洲儿童淋巴瘤和鼻咽癌。
EB病毒仅能在B淋巴细胞中增殖，可使其转化，能长期传代。被病毒感染的细胞具有EB病毒的基因组，并可产生各种抗原。在免疫抑制的情况下，EB病毒可以从被感染的细胞中脱离出来，进而感染其他细胞，引发病症。
研究人员发现，如同被EB病毒感染的人B细胞一样，LMP1+ B细胞将会被T细胞立即清除。而破坏免疫监视将导致快速、致命的淋巴细胞增殖和淋巴瘤的产生。
研究表明，LMP1在免疫监视和EB病毒感染的B细胞转化方面发挥着中心作用。这种条件性表达LMP1蛋白的小鼠模型可以用于EB病毒诱发的免疫监视和淋巴瘤的研究，并且可以验证治疗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.
