ACTIVE ANAPHYLAXIS IN IGE-DEFICIENT MICE

The IgE-triggered release of mast cell mediators in response to antige n is thought to be the primary event in immediate hypersensitivity rea ctions such as systemic anaphylaxis(1). Although mast cells and basoph ils can be activated in vitro by non-IgE stimuli(2-5), it is not known whether these triggers lead to physiological changes in vivo. To inve stigate this possibility, we generated mice with a homozygous null mut ation of the CE gene. Such mice make no IgE, but produce other immunog lobulin isotypes normally. We report that despite the IgE deficiency, sensitized mutant mice become anaphylactic on antigen challenge and di splay tachycardia and pulmonary function changes similar to those seen in wildtype animals. These responses are accompanied by vascular leak , sharply elevated plasma histamine and rapid death. IgE-independent a naphylaxis does not depend on complement activation, but, as indicated in studies using genetically immunodeficient RAG-2(-) and SCID mice, does require a functional immune system. Such results clearly demonstr ate that non-IgE pathways for hypersensitivity reactions exist in mice .