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-13, IFN-gamma or TNF-alpha. 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-gamma and TNF-alpha 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.
Tangye
S G
SG
Department of Cell and Molecular Biology, University of Technology Sydney, New South Wales, Australia.
Weston
K M
KM
Raison
R L
RL
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology*; D003432:Cross-Linking Reagents; D016207:Cytokines / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D011817:Rabbits; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000906:Antibodies; D018956:CD5 Antigens; D003432:Cross-Linking Reagents; D016207:Cytokines; D007075:Immunoglobulin M; C033027:secretory IgM; D013755:Tetradecanoylphorbol Acetate