B cell maturation in chronic lymphocytic leukemia. III. Effect of recombinant cytokines on leukemic B cell proliferation.
Proliferation and differentiation of B lymphocytes is influenced by a variety of soluble mediators. The recent cloning of various cytokines has made it possible to study the effect of molecularly defined lymphokines and other cytokines on B-cell activation. In the present study, we have analyzed the effect of several cytokines on the in vitro proliferation of highly purified leukemic B cells from patients with chronic lymphocytic leukemia (CLL). The recombinant human cytokines tested included interleukins 1, 2, 3, and 4 tumor necrosis factor-alpha (TNF-alpha) and interferon-alpha (IFN alpha), all of which are known to play a role in B-cell activation. B cells from 10 of 13 patients (all with white blood cell counts greater than 100,000/ul) did not respond to any of the cytokines tested. In contrast, B cells from 3 other patients responded well to IL-2 when preactivated for 24 h with phorbolester TPA and ionomycin. Moreover, preactivated B cells from 2 of these patients also proliferated in response to TNF-alpha, and some proliferation of unactivated B cells in response to TNF-alpha was seen in one case. Together, these results stress the clonal heterogeneity of CLL B-cell populations, and demonstrate that both IL-2 and TNF-alpha may act as a B-cell growth factor on B cells from certain CLL patients.
Nerl
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Department of Hematology, Städtisches Krankenhaus Schwabing, München, FRG.
Janssen
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Kabelitz
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D001402:B-Lymphocytes / Q000187:drug effects / Q000473:pathology*; D001685:Biological Factors / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D001685:Biological Factors; D016207:Cytokines; D011994:Recombinant Proteins