Effects of interferon-alpha on human B cell responsiveness: biphasic effects in cultures stimulated with Staphylococcus aureus.
Although interferon-alpha (IFN-alpha) has been found to be involved in the immune regulation in vivo, the effects of IFN-alpha on human B cells have not yet been clarified because of conflicting results in the literature. The present study therefore examined the effects of several subtypes of IFN-alpha (natural, alpha 1, alpha 2a, alpha 2b) on B cell responsiveness in detail by comparing different experimental conditions. Highly purified B cells from normal human individuals were cultured with Staphylococcus aureus (SA) + IL-2 or with immobilized anti-CD3-activated T4 cells in the presence or absence of IFN-alpha. IFN-alpha enhanced the immunoglobulin (Ig) production induced by immobilized anti-CD3-activated T4 cells. By contrast, IFN-alpha (5-50,000 IU/ml) suppressed the Ig production induced by SA + IL-2. The suppression by IFN-alpha was dependent on the concentration of SA. The inhibitory effects of IFN-alpha in SA-stimulated cultures were exerted in the first 72 hr of cultures and required the presence of IL-2, whereas IFN-alpha enhanced the maturation of B cells when it was added after 72 hr of cultures. The suppressive effects of IFN-alpha were overcome by addition of immobilized anti-CD3-preactivated T cells that had been treated with mitomycin C, but not by the addition of fresh T cells or soluble factors produced by activated T cells. Of interest, IFN-alpha did not inhibit the expression of IL-2R, but inhibited that of intercellular adhesion molecule-1 (ICAM-1) on B cells after stimulation with SA + IL-2, suggesting that the suppressive effects of IFN-alpha might be related to the regulation of B cell-B cell contacts through ICAM-1. There was no significant difference in effects on B cells among various subtypes of IFN-alpha. These results suggest that the effects of IFN-alpha on human B cell responsiveness may be different depending on the nature of stimulation. Moreover, the data indicate that IFN-alpha enhances the differentiation of activated B cells irrespective of the activation signals.
Department of Medicine and Physical Therapy, University of Tokyo School of Medicine, Japan.
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Oka
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Hirohata
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Inoue
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Ito
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial / Q000276:immunology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D018799:Intercellular Adhesion Molecule-1; D016898:Interferon-alpha / Q000276:immunology / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016898:Interferon-alpha; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1