IgE is recognized by two receptors: FcɛR1 expressed in mast cells and basophils, and CD23 expressed in B cells, which can be shed as soluble CD23. Allergic reactions are promoted by FcɛR1 signaling, whereas IgE abundance is regulated by CD23 binding. In the Proceedings of the National Academy of Sciences, Dhaliwal et al. report mutually exclusive allosteric modulation of IgE that governs receptor recognition. Structural analysis shows that CD23 contacts the interface formed between the Cɛ3 and Cɛ4 domains of each IgE heavy chain, whereas FcɛRI contacts the Cɛ3 dimeric interface formed by heavy-chain pairing. Receptor binding fixes the conformation of the flexible Cɛ3 domain such that recognition by the other receptor is prohibited. The topology of the CD23-IgE interaction also reveals how receptor crosslinking might occur to trigger intracellular signaling. Mutually exclusive binding thus allows greater control of receptor signaling upon recognition of IgE-allergen complexes.

Proc. Natl. Acad. Sci. USA (16 July 2012) doi:10.1073/pnas.1207278109