Basophils play a pivotal role in IgG‐ but not IgE‐mediated systemic anaphylaxis in contrast to mast cells

Anaphylaxis is a rapid‐onset, life‐threatening allergic reaction, and most commonly triggered by exposure to allergens such as insect venoms, foods, and medications. IgE and mast cells have long been associated with anaphylaxis, but recent studies suggested that an alternative pathway mediated by IgG could be more important than the classical, IgE‐mediated pathway in the elicitation of systemic anaphylaxis. Here we report in a model of penicillin shock that basophils, the least common blood cells, are dispensable for IgE‐mediated systemic anaphylaxis in contrast to mast cells, but are instead responsible for IgG1‐mediated systemic anaphylaxis. In vivo depletion of basophils but not macrophages, neutrophils, or NK cells ameliorated IgG1‐mediated passive anaphylaxis, and rescued mice from death in active systemic anaphylaxis. Upon binding of allergen‐IgG1 complexes, basophils released platelet‐activating factor (PAF), which in turn stimulated endothelial cells to increase vascular permeability. These results highlight a pivotal and non‐redundant role for basophils in vivo, and contrast two major, distinct pathways leading to allergen‐induced systemic anaphylaxis: one mediated by basophils, IgG, and PAF; the other is the classical one by mast cells, IgE, and histamine.