Common and idiosyncratic patterns of cytokine gene expression by Epstein-Barr virus transformed human B cell lines

Epstein-Barr virus (EBV) transformed human B cells proliferate indefinitely in vitro, and it has been proposed that cytokine-mediated autocrine loops contribute to the maintenance of the lymphoblastoid phenotype. We used a novel multiprobe RNase protection assay to quantify cytokine mRNA species expressed by EBV-transformed lymphoblastoid cell lines (LCL), derived either by the transformation of B cells with B95-8 or wild-type EBV or by the in vitro outgrowth of EBV-associated B cell lymphomas to identify cytokines that are commonly expressed in all LCL and thus more likely to be essential for immortalization of B cells. All 16 LCL expressed high levels of tumor necrosis factor (TNF)alpha, TNF beta, and transforming growth factor (TGF)PI mRNA, while interleukin (IL)-10 transcripts were detected in most LCL but at a lower level. Expression of IL-1 alpha; IL-1 beta, IL-6, IL-12p35, IL-12p40, IL-13 and IFN gamma mRNA was variable among the LCL tested. Granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-2, IL-4, and IL-5 mRNA were undetectable in all LCL. Furthermore, we found that IL-10, TNF alpha, and TNF beta mRNA were induced in EBV-negative B cell lines after infection with EBV. These data define common versus idiosyncratic patterns of cytokine expression by LCL and, in the former case, such cytokines as TNF alpha, TNF beta, and IL-IO emerge as strong candidates that are essential for the autocrine regulation of EBV-immortalized B cells.