INDUCTION OF LATENT MEMBRANE-PROTEIN EXPRESSION IN IN-VITRO EPSTEIN-BARR VIRUS-INFECTED LEUKEMIC B-LYMPHOCYTES BY INTERLEUKIN-4 AND ANTIBODIES TO CD40

Chronic lymphocytic leukaemia (CLL) B cells are clones representing th e mature B cell phenotype. On infection with Epstein-Barr virus (EBV) CLL cells express the EB nuclear antigen (EBNA) complex but unlike EBV -infected normal B cells they do not express LMP nor do they prolifera te or immortalize. Furthermore, EBV-CLL rapidly die by apoptosis in cu lture. In the present study we have used the B cell growth factors int erleukin 4 and antibodies to CD40 to induce activation and proliferati on of EBV-infected CLL cells. Although cell numbers did not significan tly increase, apoptosis was partially inhibited in CLL cells which exp ressed increased levels of CD23 and were activated to immunoglobulin-s ecreting lymphoblasts. Expression of LMP was induced by interleukin (I L)-4 and anti-CD40 in all five EBV-infected CLL samples examined. Howe ver, this did not enhance cell proliferation or induce immortalization . Further analysis showed that LMP could be detected 4-5 days after EB V infection, and that both IL-4 and anti-CD40 could independently indu ce LMP but that their effect was additive. These results indicate that LMP expression is dependent on B cell activation processes and that i n some circumstances full latent viral gene expression is not sufficie nt to cause B cell immortalization.