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

Baochun Zhang, Sven Kracker, Tomoharu Yasuda, Stefano Casola, Matthew Vanneman, Cornelia Hömig-Hölzel, Zhe Wang, Emmanuel 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

Research output: Contribution to journalArticlepeer-review

97 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)739-751
Number of pages13
JournalCell
Volume148
Issue number4
DOIs
Publication statusPublished - Feb 17 2012

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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