B-CLL cells experimentally infected with EBV enter DNA synthesis, produce cytokines and stimulate T-lymphocytes

Several B-chronic lymphocytic leukemia (B-CLL) clones, represented by different patients can be infected with EBV in vitro. A proportion of the cells becomes activated by the virus, but they rarely yield immortalized cell lines. We used cells from two B-CLL patients which differed in sensitivity to EBV infection. After 7 days in culture, we studied the CLL cells exposed to the B-cell activators Staphylococcus aureus, IL-2 and/or to EBV for expression of the activation markers CD23, CD39 and the adhesion and costimulatory molecules CD54 and CD80, for DNA synthesis, for production of various cytokines and for capacity to stimulate autologous and allogeneic T-lymphocytes. Generally the frequency of cells expressing cytokines in the cytoplasm correlated with the activation status of the populations and with their capacity to stimulate T-cells. It is likely that the difference between the clones with regard to sensitivity to the viral infection, is determined by the maturation state of the CLL cells. It may therefore reflect the variation in the response within a normal B-cell population. The results obtained in the present and in our earlier experiments with EBV provide information concerning the events after primary EBV infection in vivo. The T-lymphocyte stimulatory capacity of the infected CLL cells may be considered as an in vitro correlate to the syndrome of infectious mononucleosis. The detection of cytokines in the infected B-CLL cells suggests that their production by the B-blasts contributes to the level of T-lymphocytosis induced by the primary infection.