title: CD40 signaling induces interleukin-4-independent IgE switching in vivo.
abstract: 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.
authors.affiliation: DNAX Research Institute, Palo Alto, CA 94304-1104, USA.
authors.forename: W G
authors.initials: WG
authors.lastname: Ferlin
authors.forename: E
authors.initials: E
authors.lastname: Severinson
authors.forename: L
authors.initials: L
authors.lastname: Ström
authors.forename: A W
authors.initials: AW
authors.lastname: Heath
authors.forename: R L
authors.initials: RL
authors.lastname: Coffman
authors.forename: D A
authors.initials: DA
authors.lastname: Ferrick
authors.forename: M C
authors.initials: MC
authors.lastname: Howard
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D001483:Base Sequence / Q000235:genetics; D019013:CD40 Antigens / Q000276:immunology* / Q000494:pharmacology*; D005260:Female; D017578:Immunoglobulin Class Switching / Q000187:drug effects* / Q000276:immunology*; D007073:Immunoglobulin E / Q000187:drug effects* / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015398:Signal Transduction / Q000276:immunology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D015847:Interleukin-4; D007073:Immunoglobulin E