FcRL4 is an IgA receptor that primarily binds the joining chain.

Abstract

Immunoglobulin A (IgA) is a crucial component of the human immune system, and its interaction with receptors is essential for immune regulation. Fc-receptor-like 4 (FcRL4) is an IgA receptor that selectively binds systemic IgA containing the joining chain (J-chain). The molecular mechanism of this interaction has remained unclear. Here, we present a cryo-EM structure of FcRL4 complexed with the dIgA core (Fcα dimer and J-chain), revealing a 1:1 binding stoichiometry. FcRL4 primarily interacts with the J-chain but can nevertheless discriminate against J-chain-containing IgM through an entropic penalty mechanism. Our structure also explains why FcRL4 does not bind secretory IgA, as the secretory component would hinder FcRL4 binding. Functional studies indicate that FcRL4 lacks the ability to internalize IgA or IgA immune complex. These findings provide fresh insights into IgA biology.