CD40 SIGNALING INDUCES INTERLEUKIN-4-INDEPENDENT IGE SWITCHING IN-VIVO

T cell-deficient T cell receptor (TCR) beta(-/-) x TCR delta(-/-) knoc kout mice lack circulating IgE and fail to produce antigen-specific Ig E in response to stimulation with T cell-dependent antigens. We show h ere that these animals are able to produce significant levels of circu lating polyclonal IgE when injected with an agonistic anti-mouse CD40 monoclonal antibody. CD40-mediated induction of circulating polyclonal IgE in T cell-deficient mice was only partially reduced when the anim als were co-treated with neutralizing anti-interleukin-4 (IL-4) antibo dy. The IL-4 independence of this response was further supported by ex periments showing that anti-CD40 antibodies induced circulating IgE wh en injected into IL-4 knockout mice, and sterile RNA epsilon transcrip t production when cultured with purified B cells from the same mice. T hese data strongly suggest that CD40 signaling causes IL-4-independent IgE switching in mice.