The role of IL-10 in human B cell activation, proliferation, and differentiation.
Recent studies have disclosed variable effects of IL-10 on viabilities of human B lineage cells. Thus, IL-10 has been shown to prevent apoptosis of germinal center B cells, whereas IL-10 has been found to induce apoptosis of B-chronic lymphocytic leukemia cells, suggesting the possibility that the effects of IL-10 might be different depending on the state of activation of B cells. The current studies therefore examined in detail the regulation of the survival of human peripheral blood B cells by IL-10 and its relevance to Ig production. Highly purified B cells from healthy adult individuals were cultured with Staphylococcus aureus (SA) Cowan I in the presence or absence of IL-10. When IL-10 was present during the initial activation of B cells with SA, IL-10 facilitated the apoptosis of SA-activated B cells, as determined by staining with propidium iodide, followed by analysis with flow cytometry, thus resulting in very modest IgM production. IL-2 prevented the IL-10-mediated progression of the apoptosis of SA-activated B cells during the initial activation, and thus restored the further differentiation of these B cells into Ig secreting cells. By contrast, IL-10 rather rescued SA-activated B cells from apoptosis and thus supported the differentiation of these B cells without any influences of IL-2, when it was added after 72 h of culture. Of note, cyclosporin A prevented the IL-10-mediated promotion of the apoptosis of SA-activated B cells, thus resulting in the marked enhancement of IgM production of B cells stimulated with SA + IL-10. Finally, the promotion or prevention of the IL-10-mediated apoptosis was correlated with the expression of Bcl-2 oncoprotein in SA-activated B cells. These results indicate that the effects of IL-10 are different depending on the state of activation of B cells after ligation of Ag receptors. Thus, the data have demonstrated that IL-10 during the initial activation delivers negative signals that promote the apoptosis of B cells, whereas IL-10 supports the differentiation of B cells in the complete absence of IL-2 during the subsequent responses following activation. These results therefore emphasize unique biphasic effects of IL-10 on human B cell responsiveness in determining the outcome of humoral immune responses.
Itoh
K
K
Second Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Hirohata
S
S
D000328:Adult; D000942:Antigens, Bacterial / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000187:drug effects; D016753:Interleukin-10 / Q000037:antagonists & inhibitors / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology
D000942:Antigens, Bacterial; D007075:Immunoglobulin M; D016753:Interleukin-10; D016572:Cyclosporine