
<ArticleTitle>Antagonistic effects of <prot>c-myc</prot> and Epstein-Barr virus latent genes on the phenotype of human B cells.</ArticleTitle>
<AbstractText>Epstein-Barr virus (EBV) immortalized cells and Burkitt lymphoma cells have a completely different growth pattern and phenotype. EBV immortalized cells express a set of 11 viral genes to accommodate B cell activation and proliferation, whereas EBV-positive Burkitt lymphoma cells highly express the <prot>c-myc</prot> oncogene that is activated through translocation into 1 of the immunoglobulin loci and <prot>EBNA1</prot> as the only viral protein. We have developed a primary human B cell line conditionally immortalized by Epstein-Barr virus in which the viral gene program responsible for the induction of proliferation can be switched on and off by the addition or withdrawal of estrogen (cell line EREB2-5). Starting from this cell line we have generated 2 daughter cell lines that proliferate in a <prot>c-myc</prot> dependent fashion, 1 with a highly active exogenous <prot>c-myc</prot> gene (cell line A1) and 1 with a regulatable <prot>c-myc</prot> gene that can be switched on by withdrawal and switched off by addition of tetracycline (cell line P493-6). The comparison of the 3 cell lines has allowed us to dissect the contribution of <prot>c-myc</prot> and EBV genes to the regulation of the growth pattern and expression of cell surface molecules. We show that <prot>MYC</prot> and <prot>EBNA2</prot> (and their respective target genes) have opposing effects on the expression of several surface markers involved in B cell activation. We show that <prot>MYC</prot> contributes to the phenotype of Burkitt lymphoma cells by upregulating <prot>CD10</prot> and <prot>CD38</prot> and downregulating activation markers. The phenotype of the cells is determined on one hand by the absence of the viral gene products <prot>EBNA2</prot> and <prot>LMP1</prot> that mediate the phenotype of activated lymphoblasts and to a lesser extent by an active contribution of the <prot>c-myc</prot> gene.</AbstractText>
