IgE in the Regulation of Adaptive Immune Responses

ABSTRACT Immunoglobulin E (IgE) plays a dual role in the immune system, providing protection against pathogens while also mediating pathological hypersensitivity reactions. Its function is mainly studied in the context of immediate inflammatory responses, where IgE‐sensitized effector cells, such as mast cells and basophils, are triggered by a cross‐linking antigen. An often‐overlooked feature of IgE biology is its strong ability to boost secondary adaptive immune responses, thus acting as a physiological adjuvant. The regulation of these responses is influenced by various factors, including the primary Ig structure, post‐translational modifications such as glycosylations, structural properties of the antigens, and the interaction of IgE with immune receptors. Interestingly, IgE not only generates antigen‐specific immune responses, but also IgE‐specific autoimmune responses. Natural IgG anti‐IgE autoantibodies circulate at surprisingly high levels, even in healthy individuals, contributing to the regulation of IgE serum levels and its interaction with receptors. Understanding these emerging concepts, beyond a singular focus on initial IgE production and immediate effector cell activation, could contribute to a better understanding of the immunological functions of IgE. In this review, we aim to provide an overview of current knowledge on IgE immunogenicity. Many open questions remain on the negative and positive feedback mechanisms by which IgE regulates the adaptive immune response, and we hope to inspire future research into the mechanisms underlying IgE‐regulated immune responses and their potential implications for therapeutic strategies in hypersensitivity diseases.