INFECTION OF LEUKEMIC B-LYMPHOCYTES BY EPSTEIN-BARR-VIRUS

Epstein-Barr virus (EBV) infection of B lymphocytes in vitro gives ris e to immortalized lymphoblastoid cell lines. Previous reports have sho wn that chronic lymphocytic leukaemia (CLL) cells, although infectable by EBV, are resistent to immortalization (1-4), although a small numb er of CLL cell lines have been reported (5-7). In the present study we have analysed early events occurring after EBV infection in 16 CLL sa mples. Out of 16 samples, 15 could be infected by the virus and expres sed the full EB viral nuclear antigen (EBNA) complex but only one out of 16 expressed the latent membrane protein (LMP). The five CLLs in wh ich we could investigate the presence of viral episomes showed circula rized EBV by 16 hours after infection. The sequence of EBNA expression and genome circularization mirrored that seen in normal B cells, alth ough genome amplification was not detected. The only CLL sample which expressed LMP after EBV infection was induced to proliferate for 2-3 w eeks, but no cell line was established. Immortalized cell lines were o btained from three out of 16 samples tested, but all were polyclonal f or light chain expression and had arisen from the CD5-negative, normal B-cell population. Thus the inability of EBV to induce proliferation of most CLL cells correlated with the absence of LMP expression which is invariably expressed during immortalization of normal 8 cells. This novel type of restricted gene expression could be compatible with eva sion of host immune responses and consequent long-term survival of the cell in vivo.