Activation and immortalization of leukaemic B cells by Epstein-Barr virus

Abstract

We have studied the responses of chronic leukaemic B cells to infection by Epstein-Barr virus (EBV). Our results define one population of B lymphocytes, represented by prolymphocytic leukaemic (PLL) cells, which are highly susceptible to immortalization by EBV. Another B-cell type, represented by chronic lymphocytic leukaemic (CLL) cells, can be readily infected by the virus but is resistant to immortalization. Comparative studies of viral and cellular related events early after infection in these 2 cell types reveal that both express the EB viral nuclear antigen (EBNA) complex, but the immortalization-resistant CLL cells fail to express the latent membrane protein (LMP), which can be detected in PLL cells 48 hr after infection. Circularization of the linear viral genome could be detected at 7 days post infection in the PLL cells, but only in 2 out of 4 CLL cells tested. Both CLL and PLL cells show increased surface expression of CD23 and HLA-DR molecules after infection but, whereas PLL cells show an increase in size, together with RNA and DNA synthesis indicative of cell cycle progression, CLL cells appear to be arrested in the G1/S phase of the cycle. The results suggest that the outcome of infection by EBV is determined by the nature of the target cell rather than by random virus-related events. The correlation between the block in immortalization of CLL cells and their failure to express LMP suggests that expression of this protein is essential for in vitro immortalization of B cells. The failure to detect circularization in some EBV-infected CLL cells suggests that this, as well as LMP expression, may be dependent on prior activation of the B cell by EBV, an event which may vary between the different CLL samples tested.