Protein kinase C regulates secretion of lymphotoxin (LT/TNFβ) and TNFα by human EBV-transformed B cells

Abstract

Epstein-Barr virus (EBV)–transformed cell lines constitutively secrete lymphotoxin (LT/TNFβ) and not tumor necrosis factor-α (TNFα). To analyze the cellular processes that regulate LT and TNFα secretion by lymphoblastoid cell lines, we studied the role of two signal transduction pathways leading to either protein kinase C (PK-C) or PK-A activation. We demonstrate that PK-C activation, either after cross-linking of surface Ig or by direct activation with phorbolester, leads to increased production of both LT and TNFα, whereas no prominent role for PK-A was found. Interleukin (Il)-4 was found to synergize with PK-C activation in raising levels of secreted LT and TNFα. Increased levels of LT and TNFα did not correlate with augmented levels of immunoglobulin secreted by the cell lines nor with improved proliferation. These observations demonstrate that EBV B cells respond to B cell activation signals leading to PK-C activation with increased production of both LT and TNFα. It is, however, unlikely that these molecules serve as autostimulatory factors for EBV B cells, but in contrast might play a role in downregulation of biological functions in these cells.