Diversity in inhibitory effects of IFN-gamma and IFN-alpha A on the induced DNA synthesis of a hairy cell leukemia B lymphocyte clone reflects the nature of the activating ligand.
A hairy cell leukemia population was used as a clonal model for studying the direct immunomodulatory effects of recombinant interferon-alpha A (rIFN-alpha A) and rIFN-gamma on human B-cell proliferation. The leukemic cell population KON was notably quiescent when incubated in medium alone but was induced to significant in vitro DNA synthesis when cultured with any of four activators of human B cells: anti-IgM antibody, Staphylococcus aureus cells (SAC), phorbol myristate acetate (PMA), or B-cell growth factor (BCGF). While both rIFN-gamma and rIFN-alpha A exhibited suppressive effects on these responses, their inhibitory patterns were distinct and reciprocal. Thus, rIFN-gamma exclusively suppressed anti-IgM-and SAC-induced leukemic DNA synthesis, and rIFN-alpha A significantly suppressed only PMA- and BCGF-induced DNA synthesis. The effects of the rIFN preparations were ablated in the presence of IFN type-specific monoclonal antibodies. Kinetic analyses and pulsing studies revealed that inhibition was most notable when cells were exposed concomitantly to IFN and the activating ligand. That the diverse effects of IFN-gamma and IFN-alpha A are manifested on a single B-cell clone was confirmed by Southern blot analysis of restriction enzyme-digested KON cell DNA with a JH-specific probe. These studies suggest that the therapeutic potential of the two types of IFN may be influenced by the nature of the extracellular ligands in the leukemic mileau that promote leukemic clonal expansion.
D000937:Antigen-Antibody Reactions; D001402:B-Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D002999:Clone Cells; D004247:DNA / Q000096:biosynthesis; D015322:Gene Rearrangement, B-Lymphocyte; D006801:Humans; D007144:Immunoglobulin J-Chains / Q000235:genetics; D007370:Interferon Type I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D015847:Interleukin-4; D007378:Interleukins / Q000494:pharmacology; D007943:Leukemia, Hairy Cell; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011994:Recombinant Proteins; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007144:Immunoglobulin J-Chains; D007370:Interferon Type I; D007378:Interleukins; D008024:Ligands; D011947:Receptors, Antigen, B-Cell; D011994:Recombinant Proteins; D015847:Interleukin-4; D007371:Interferon-gamma; D004247:DNA; D013755:Tetradecanoylphorbol Acetate