EBV counteracts IL-21-induced apoptosis in an EBV-positive diffuse large B-cell lymphoma cell line

Previously, interleukin (IL)-21 has been found to induce apoptosis by activating the signal transducer and activator of transcription 3 (STAT3) and concomitant upregulation of c-Myc in diffuse large B-cell lymphoma (DLBCL) lines with unknown Epstein-Barr virus (EBV) status. Here, as a first approach toward the characterization of the role of EBV in DLCBL, the EBV gene expression and the IL-21 sensitivity of the EBV-positive DLBCL line, Farage, have been examined. It was found that, surprisingly, despite c-Myc upregulation, IL-21 induced cell proliferation rather than apoptosis in Farage. Expression of a dominant-negative EBNA1 mutant and the consecutive downregulation of EBV gene expression antagonized the IL-21-induced proliferation of Farage and increased apoptosis. These findings reveal a previously unknown role of EBV in DLBCL that is of possible relevance for the current attempt to use IL-21 in therapy.