Interleukin 5 enhances interleukin 4‐induced IgE production by normal human B cells. The role of soluble CD23 antigen

Abstract

Interleukin 4 (IL 4)-induced IgE production by peripheral blood lymphocytes and tonsil cells from normal donors was enhanced in a dose-dependent fashion by IL5. IL5 tested alone was not effective. The synergistic effects of IL5 were most pronounced at suboptimal IL4 concentrations, whereas at saturating IL4 concentrations (200-300 U/ml), IL5 had no effect. Interferon-γ (IFN-γ) and F(ab′)₂ fragments of monoclonal antibody 25 directed against the CD23 antigen, that blocked IL4-induced IgE synthesis, also inhibited the production of IgE in the presence of combinations of IL4 and IL5, indicating that IL5 potentiates the activation pathway through which IL4 induces IgE production. In contrast, IL4 (50 U/ml) blocked IL5-induced IgA synthesis. IL 5 was ineffective in inducing the release of soluble CD23 (sCD23), but in the presence of IL4 an enhanced release of sCD23 was observed, provided IL4 was present at suboptimal concentrations. IFN-γ completely blocked sCD23 release induced by IL4 and IL5. These results demonstrate that there is a strong quantitative correlation between sCD23 release and induction of IgE synthesis. sCD23 fractionated from the Epstein-Barr virus-transformed B cell line RPMI 8866 was ineffective in inducing IgE production. However, sCD23 acted synergistically with suboptimal concentrations of IL4. sCD23 did not modulate the IgE response at saturating concentrations of IL4. Collectively, these data indicate that sCD23 plays an important regulatory role in the modulation of IL4-induced IgE synthesis mediated by IFN-y and IL5.