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IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter
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IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter
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IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter
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Journal Article
IL-21 imposes a type II EBV gene expression on type III and type I B cells by the repression of C- and activation of LMP-1-promoter
2010
Overview
Epstein-Barr virus (EBV) is associated with a variety of human tumors. Although the EBV-infected normal B cells in vitro and the EBV-carrying B cell lymphomas in immunodeficient patients express the full set of latent proteins (type III latency), the majority of EBV-associated malignancies express the restricted type I (EBNA-1 only) or type II (EBNA-1 and LMPs) viral program. The mechanisms responsible for these different latent viral gene expression patterns are only partially known. IL-21 is a potent B cell activator and plasma cell differentiation-inducer cytokine produced by CD4⁺ T cells. We studied its effect on EBV-carrying B cells. In type I Burkitt lymphoma (BL) cell lines and in the conditional lymphoblastoid cell line (LCL) ER/EB2-5, IL-21 potently activated STAT3 and induced the expression of LMP-1, but not EBNA-2. The IL-21-treated type I Jijoye M13 BL line ceased to proliferate, and this was paralleled by the induction of IRF4 and the down-regulation of BCL6 expression. In the type III LCLs and BL lines, IL-21 repressed the C-promoter-derived and LMP-2A mRNAs, whereas it up-regulated the expression of LMP-1 mRNAs. The IL-21-treated type III cells underwent plasma cell differentiation with the induction of Blimp-1, and high levels of Ig and Oct-2. IL-21 might be involved in the EBNA-2-independent expression of LMP-1 in EBV-carrying type II cells. In light of the fact that IL-21 is already in clinical trials for the treatment of multiple malignancies, the in vivo modulation of EBV gene expression by IL-21 might have therapeutic benefits for the EBV-carrying malignancies.
Publisher
National Academy of Sciences,National Acad Sciences
Subject
/ Cell Division - drug effects
/ Cells
/ Epstein-Barr Virus Nuclear Antigens - pharmacology
/ Gene Expression Regulation, Viral - drug effects
/ Herpesvirus 4, Human - genetics
/ Humans
/ Immunoglobulin J Recombination Signal Sequence-Binding Protein - drug effects
/ Immunoglobulin J Recombination Signal Sequence-Binding Protein - genetics
/ Lymphoma
/ Lymphoma, B-Cell - immunology
/ Lymphoma, B-Cell - pathology
/ patients
/ Plasma
/ Promoter Regions, Genetic - drug effects
/ Proteins
/ Tumors
/ Viral Matrix Proteins - drug effects
/ Viral Matrix Proteins - genetics
/ Viral Matrix Proteins - pharmacology
/ Viral Proteins - pharmacology
/ Viruses
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