Effects of n-butyrate and phorbol ester (TPA) on induction of Epstein-Barr virus antigens and cell differentiation.

N-Butyrate, an effective inducer of synthesis of Epstein-Barr virus (EBV) antigens in virus-producer P3HR-1 cells, has recently been shown (2) to induce morphological differentiation towards plasma cell in nonproducer Raji cells. The effects of n-butyrate and 12-O-tetradecanoylphorbol-13-acetate (TPA) on both EBV-antigen induction and cell differentiation in two virus-nonproducer lymphoblastoid cell lines, Raji and NC37, were now studied. The following observations were made (1). On its own either drug induced 1-2 per cent of cells to EBV-early-antigen positivity in both lines; their mixture induced 35 and 15 per cent positive cells in Raji and NC37 respectively (2). In Raji, n-butyrate induced about 80 per cent of cells to differentiate to plasmablast or plasma cell morphology, whereas TPA only induced the early stages of differentiation in 8 per cent of cells; a mixture of both inducers produced a similar effect as TPA alone. The addition of TPA alone or butyrate-TPA mixture led to some cellular alterations resembling virus-specific changes in virus-producer cell lines. In NC37, either drug alone or their mixture drove 13 per cent of cells to differentiate into plasmablasts or earlier stages of differentiation. In the presence of TPA protrusions and "loops" were seen on cell surfaces. Evidently, the stage of differentiation at which B-lymphoblastoid cell lines have been arrested can be changed in vitro. However, cell-line dependent and inducer-dependent differences in the differentiation response were apparent.