Figure 2.

Interplay between FcRn and low-affinity FcγRs in shuttling antigen-ICs across epithelial barriers. 1. In the intestine, IgG antibodies can bind to FcRn expressed at the basolateral cell membrane of epithelial cells. These antibodies will then be internalized and shuttled bound to FcRn with high affinity inside the acidic microenvironment of endosomes. 2. On the apical (gut lumen oriented) side of the epithelial cell, due to the more neutral pH and consequently, reduced affinity of FcRn for IgG, these IgG antibodies are released, and can subsequently bind to soluble protein antigen. Alternatively (orange arrow), FcRn can shuttle monomeric IgGs back to the tissue interstitium (IgG recycling), a process preventing IgG degradation in sour compartments especially in APCs. 3. Luminal IgG-ICs can be internalized and shuttled, via endosomal vesicles, by binding to FcRn, through the epithelial cell soma. 4. These IgG-ICs are then released at the basolateral cell surface to the tissue interstitium, where they bind to low-affinity FcγRs on the cell surface of APCs.