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 indefin itely in vitro, and it has been proposed that cytokine-mediated autocr ine loops contribute to the maintenance of the lymphoblastoid phenotyp e. We used a novel multiprobe RNase protection assay to quantify cytok ine mRNA species expressed by EBV-transformed lymphoblastoid cell line s (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 l ymphomas to identify cytokines that are commonly expressed in all LCL and thus more likely to be essential for immortalization of B cells. A ll 16 LCL expressed high levels of tumor necrosis factor (TNF)alpha, T NF beta, and transforming growth factor (TGF)PI mRNA, while interleuki n (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 a nd IFN gamma mRNA was variable among the LCL tested. Granulocyte-macro phage colony-stimulating factor (GM-CSF), IL-2, IL-4, and IL-5 mRNA we re undetectable in all LCL. Furthermore, we found that IL-10, TNF alph a, and TNF beta mRNA were induced in EBV-negative B cell lines after i nfection with EBV. These data define common versus idiosyncratic patte rns of cytokine expression by LCL and, in the former case, such cytoki nes as TNF alpha, TNF beta, and IL-IO emerge as strong candidates that are essential for the autocrine regulation of EBV-immortalized B cell s.