Differential regulation of umbilical cord blood and leukemic B cells by interferon-alpha (IFN-alpha): observations in cultured cells.
The exact mechanism of the beneficial therapeutic action of interferon-a (IFN-alpha) in B-cell-lineage malignancies has not been adequately explained. Here we report on the differential effect of IFN-alpha2b on non-malignant B cells of umbilical cord blood and leukemic B-cell lines JY, BL-41 and BCBL-1. Leukemic cell proliferation was characterized by colony assay, whereas apoptosis was investigated by flow cytometry of propidium iodide-stained cells. The degree of differentiation was evaluated by measuring the expression level of Fcgamma receptor-II (FcgammaRII) labeled with anti-CD32-FITC monoclonal antibody using flow cytometry. IFN-alpha protected umbilical cord blood CD19-positive B lymphocytes from apoptotic cell death in vitro. IFN-alpha significantly decreased colony formation of all three cell lines, and in contrast to normal cells, induced apoptosis in JY and BL-41 and excessive necrosis in HHV-8 infected BCBL-1 cells. FcgammaRII was upregulated both in normal and in leukemic B cells as indicated by an increase both in the proportion of CD32-positive cells and the mean fluorescence intensity. From our results it seems that antiproliferative, apoptotic and differentiative effects of IFN-alpha are interrelated but distinct cellular events, which are differentially regulated in normal, leukemic and virus-infected cells of the B-cell lineage.
Szegedi
István
I
Department of Pediatrics, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary.
Kiss
Csongor
C
Karászi
Eva
E
Vámosi
György
G
Szöllôsi
János
J
Kovács
Péter
P
Benkô
Ilona
I
D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology*; D015448:Leukemia, B-Cell / Q000276:immunology / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D017452:Receptors, IgG / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D017452:Receptors, IgG; D011994:Recombinant Proteins