Impact of the mucosal milieu on antibody responses to allergens

Respiratory and digestive mucosal surfaces are continually exposed to common environmental antigens, which include potential allergens. Although innocuous in healthy individuals, allergens cause allergy in predisposed subjects and do so by triggering a pathologic T_H2 cell response that induces IgE class switching and somatic hypermutation in allergen-specific B cells. The ensuing affinity maturation and plasma cell differentiation lead to the abnormal release of high-affinity IgE that binds to powerful FcεRI receptors on basophils and mast cells. When cross-linked by allergen, FcεRI-bound IgE instigates the release of prestored and de novo-induced proinflammatory mediators. Aside from causing type I hypersensitivity reactions underlying allergy, IgE affords protection against nematodes or venoms from insects and snakes, which raises questions as to the fundamental differences between protective and pathogenic IgE responses. In this review, we discuss the impact of the mucosal environment, including the epithelial and mucus barriers, on the induction of protective IgE responses against environmental antigens. We further discuss how perturbations of these barriers may contribute to the induction of pathogenic IgE production.