CD40 signaling induces interleukin-4-independent IgE switching in vivo

• Published in: European journal of immunology Vol. 26; no. 12; p. 2911
• Main Authors: Ferlin, W G, Severinson, E, Ström, L, Heath, A W, Coffman, R L, Ferrick, D A, Howard, M C
• Format: Journal Article
• Language: English
• Published: Germany 01.12.1996
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Base Sequence - genetics; CD40 Antigens - immunology; CD40 Antigens - pharmacology; Female; Immunoglobulin Class Switching - drug effects; Immunoglobulin Class Switching - immunology; Immunoglobulin E - drug effects; Immunoglobulin E - immunology; Interleukin-4 - immunology; Interleukin-4 - pharmacology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction - immunology; Transcription, Genetic - drug effects
• ISSN: 0014-2980
• DOI: 10.1002/eji.1830261216

T cell-deficient T cell receptor (TCR) beta-/- x TCR delta-/- knockout mice lack circulating IgE and fail to produce antigen-specific IgE in response to stimulation with T cell-dependent antigens. We show here that these animals are able to produce significant levels of circulating 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 animals were co-treated with neutralizing anti-interleukin-4 (IL-4) antibody. The IL-4 independence of this response was further supported by experiments showing that anti-CD40 antibodies induced circulating IgE when injected into IL-4 knockout mice, and sterile RNA epsilon transcript production when cultured with purified B cells from the same mice. These data strongly suggest that CD40 signaling causes IL-4-independent IgE switching in mice.