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Immune surveillance and therapy of lymphomas driven by Epstein-Barr-Virus protein LMP1 in a mouse model

Item Type:Article
Title:Immune surveillance and therapy of lymphomas driven by Epstein-Barr-Virus protein LMP1 in a mouse model
Creators Name:Zhang, B. and Kracker, S. and Yasuda, T. and Casola, S. and Vanneman, M. and Hömig-Hölzel, C. and Wang, Z. and Derudder, E. and Li, S. and Chakraborty, T. and Cotter, S.E. and Koyama, S. and Currie, T. and Freeman, G.J. and Kutok, J.L. and Rodig, S.J. and Dranoff, G. and Rajewsky, K.
Abstract: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.
Keywords:Animal Disease Models, B-Lymphocytes, Human Herpesvirus 4, Immunologic Surveillance, Immunotherapy, Inbred BALB C Mice, Inbred C57BL Mice, Lymphoma, NK Cell Lectin-Like Receptor Subfamily K, T-Lymphocytes, Viral Matrix Proteins, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:148
Number:4
Page Range:739-751
Date:17 February 2012
Official Publication:https://doi.org/10.1016/j.cell.2011.12.031
PubMed:View item in PubMed

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