IN-VITRO ACTIVATION OF LEUKEMIC B-CELLS BY INTERLEUKIN-4 AND ANTIBODIES TO CD40

Chronic lymphocytic leukaemia (CLL) B cells have the phenotype of matu re, partially activated B cells, but are relatively resistant to stimu lation through cell-surface receptors with agents such as antibodies t o immunoglobulin M. In the present study we have shown that culture of CLL cells with interleukin-4 (IL-4) and antibodies to CD40 caused sig nificant DNA synthesis as assessed by incorporation of thymidine. This effect was largely mediated by antibody binding to CD40, a molecule k nown to induce B-cell activation and to mediate survival signals to ge rminal centre B cells. Epstein-Barr virus (EBV) infection of CLL cells stimulated with IL-4 and anti-CD40 did not affect the state of differ entiation of the cell, augment the proliferative capacity, prolong cel l survival or cause virus-driven immortalization.