Cytokines and cross-linking of sIgM augment PMA-induced activation of human leukaemic CD5+ B cells
Purified leukaemic CD5+ B cells obtained from patients with B cell chronic lymphocytic leukaemia (B-CLL) undergo activation and differentiation following in vitro stimulation with optimal concentrations of the phorbol ester PMA. This paper examines the ability of exogenous cytokines, anti-Ig antibodies, or combinations of these, to enhance or replace the activation signal provided by PMA to different populations of leukaemic B cells. Proliferation induced by PMA was enhanced 2–20-fold when the cells were co-cultured with either anti-Ig, IL-2, IL-4. IL-I3. IFN- or TNF-. Moreover, the combination of anti-Ig. PMA and any one of the above cytokines further enhanced proliferation. Anti-Ig and exogenous cytokines were also capable of inducing proliferation in leukaemic B cells cultured with a non-mitogenic concentration of PMA. When taken together with the finding that IL-2, IL-4, IL-13, IFN- and TNF-a prevent in vitro apoptosis of leukaemic CD5+ B cells, the results presented here suggest that these cytokines, in conjunction with signals delivered via sig, may play a role in the proliferation of leukaemic B cells in vivo and. consequently, the pathogenesis of B-CLL.