Homologous T and B cells immortalized in vitro by the Epstein-Barr virus exhibit differential genetical and functional features

Abstract

After in vitro EBV infection of peripheral blood lymphocytes (PBL), we previously obtained IL-2-independent T-cell lines expressing EBNA1 and LMP1 viral latent genes. One tumorigenic clone, NC5, was further characterized for chromosomal abnormalities, rearrangement and expression of oncogenes, and constitutive or induced activation of cellular transduction pathways. NC5 as well as TC cells derived from an NC5-induced tumor exhibited the same few chromosomal abnormalities absent in normal PBL and B-cell lines (LCLs) from the same donor. No rearrangement or altered expression of C-MYC, BCL-2 and NF-KB2 oncogenes could be detected. In contrast, we found high levels of BCL-X and thioredoxin (TRX), as markers of EBV infection or T-cell activation/transformation status. No constitutive activation of NF-kappa B or STAT transcriptional complexes was observed in these cells. For NF-kappa B, this was in apparent contradiction with its reported inducibility mediated by LMP1, taking into account that NF-kappa B was still inducible by TNF alpha or PMA and ionomycin. Our results highlight independence of EBV protein-mediated transformation towards classical cellular pathways in T-lymphocytes.