Keeping virus-driven lymphomas in check

Abstract

Epstein–Barr virus (EBV) is rapidly cleared by the immune system, but it can persist in some cells for life. Under conditions of immunosuppression, B cells that are latently infected with EBV can undergo marked proliferation and malignant transformation. EBV latent membrane protein 1 (LMP1) is essential for the transformation of human B cells. Here, the authors generated a mouse model in which all B cells expressed LMP1. LMP1 + B cells were efficiently deleted by T cells in immunocompetent animals, but they underwent marked clonal expansion and formed large B cell lymphomas in immunocompromised animals. Both CD4 + and CD8 + T cells contributed to immune surveillance of LMP1 + B cells. Natural killer (NK) cells were also activated by LMP1 + B cells, which expressed ligands for the NK cell receptor NKG2D. Indeed, treatment of tumour-bearing mice with an NKG2D–Fc fusion protein caused efficient lysis of LMP1 + tumour cells, suggesting a possible new therapy for EBV-driven B cell lymphomas. ORIGINAL RESEARCH PAPER Zhang, B. et al. Immune surveillance and therapy of lymphomas driven by Epstein-Barr virus protein LMP1 in a mouse model. Cell 148, 739–751 (2012)