In vitro activation of leukaemic B cells by interleukin-4 and antibodies to CD40.

Chronic lymphocytic leukaemia (CLL) B cells have the phenotype of mature, partially activated B cells, but are relatively resistant to stimulation through cell-surface receptors with agents such as antibodies to immunoglobulin M. In the present study we have shown that culture of CLL cells with interleukin-4 (IL-4) and antibodies to CD40 caused significant DNA synthesis as assessed by incorporation of thymidine. This effect was largely mediated by antibody binding to CD40, a molecule known to induce B-cell activation and to mediate survival signals to germinal centre B cells. Epstein-Barr virus (EBV) infection of CLL cells stimulated with IL-4 and anti-CD40 did not affect the state of differentiation of the cell, augment the proliferative capacity, prolong cell survival or cause virus-driven immortalization.