Regulation of IgE synthesis by T cells and cytokines

Abstract

Human IgE synthesis is tightly regulated by cytokines. IgE production by normal B cells is specifically induced by IL-4, but requires additional, yet to be defined, signals that are provided by CD 4 + T cells. Single surface IgM + B cells can be induced to proliferate and switch to IgG 4 and IgE producing cells, indicating that the induction of IgE synthesis by IL-4 and CD 4 + T cells reflects direct isotype switching. Although IL-4 is the sole inducing cytokine of IgE synthesis known thus far, multiple cytokines modulate IL-4 induced IgE synthesis in vitro. IFN-α, IFN-γ TGF-β and IL-10 are inhibitory, whereas IL-5, IL-6 and TNF-α act synergistically with IL-4. Results obtained with animal models, as well as from clinical studies in the human have indicated that IL-4, IFN-α and IFN-γ are operational in vitro. Cocultivation of B cells with allergen-specific CD 4 + T cell clones producing high levels of IL-4 and IL-5, but normal to undetectable levels of IL-2 and IFN-γ, following activation resulted in the synthesis of IgE, in the absence of exogenously added IL-4. These results indicate that aberrant ratio's of IL-4 and IFN-γ production are sufficient for induction of IgE synthesis in vitro. The notion that an imbalance of cytokine production may account for the high serum IgE levels in allergic patients was supported by the finding that IFN-α and IFN-γ administered to patients with the hyper IgE syndrome resulted in a selective reduction in serum IgE levels which was accompanied by an improvement of clinical symptoms.