Significance of IL-15 in IL-4 induced B cell activation, immunoglobulin isotype class switching and IgE production (IRM10P.613)

Abstract IgE-mediated immune responses contribute to the pathogenesis of allergic diseases. Despite their significant role in immune biology, the factors that produce and regulate IgE responses are yet to be established. Notably, IL-4 is a well-established cytokine involved in immunoglobulin (Ig) isotype class switching and IgE production. However we recently observed that IL-15 over expression in mice (pharmacologically or by transgene insertion) induces IgE levels. Therefore we hypothesized that IL-15 might have some role in B cells proliferation, activation, Ig isotype class switching and IgE production. Accordingly we examined the level of IgE, B cells and Ig isotype class switching in response to IL-15 using ELISA, real time qPCR and flowcytometric analysis. Our initial in vitro data show proliferation, activation and induced Ig class switching genes in purified B cells following rIL-15 treatments. Further, we show reduced IgE levels in IL-15 gene-deficient mice compared to Balbc mice following Aspergillus fumigatus exposure. Furthermore we examined the role of IL-15 in IL-4 mediated IgE production. We observed that IL-4 gene-deficient mice have increased IgE levels and B cell activation following intravenous administration of IL-15 compared to saline. However, significant IgE levels were observed following IL-15 treatment in Balbc mice compared to IL-4 gene-deficient mice.Together we conclude that IL-15 is required for the IL-4 induced B cell activation and allergen induced IgE.