IgG trafficking in the adult pig small intestine: one- or bidirectional transfer across the enterocyte brush border?

Abstract

Immunoglobulin G (IgG) transfer in opposite directions across the small intestinal brush border serves different purposes in early life and in adulthood. In the neonate, maternal IgG is taken up from the gut lumen into the blood, conferring passive immunity to the offspring, whereas in the adult immunoglobulins, including IgG made by plasma cells in the lamina propria, are secreted via the brush border to the lumen as part of the mucosal defense. Here, IgG has been proposed to perform a luminal immune surveillance which eventually includes a reuptake through the brush border as pathogen-containing immune complexes. In the present work, we studied luminal uptake of FITC-conjugated and gold-conjugated IgG in cultured pig jejunal mucosal explants. After 1 h, binding to the brush border was seen in upper crypts and lower parts of the villi. However, no endocytotic uptake into EEA-1-positive compartments was detected, neither at neutral nor acidic pH, despite an ongoing constitutive endocytosis from the brush border, visualized by the polar tracer CF594. The 40-kDa neonatal Fc receptor, FcRn, was present in the microvillus fraction, but noteworthy, a 37 kDa band, most likely a proteolytic cleavage product, bound IgG in a pH-dependent manner more efficiently than did the full-length FcRn. In conclusion, our work does not support the theory that bidirectional transfer of IgG across the intestinal brush border is part of the luminal immune surveillance in the adult.

Maternal Vaccination. Immunization of Sows during Pregnancy against ETEC Infections

“…In the neonate, FcRn allows the ingested maternal IgG to be taken up from the gut lumen into the blood (see above, passive immunity). In the adult, the IgG produced in the intestinal Peyer’s patches uses this route to be released to the gut lumen as part of the mucosal defense [ 20 , 23 ]. After “gut closure”, milk polymeric IgA and IgM use the pIgR (polymeric immunoglobulin receptor) to cross the epithelial cells and reach the blood stream, or may stay in the gut lumen for surveillance.…”

Short FcRn-Binding Peptides Enable Salvage and Transcytosis of scFv Antibody Fragments

“…When IgG or albumin is taken up by polarized epithelial or endothelial cells, they are packaged into endosomes, which acidify as they traffic through the cell. 15 In this low-pH environment, histidines on albumin and the IgG Fc domain are protonated and binding to FcRn and its cognate light-chain β2 microglobulin (β2m) is enabled. 16 Association of β2m with FcRn is required for binding with IgG and albumin.…”

“…In addition to mediating immune effector functions such as recruiting humoral and cellular responses, the Fc domain is also responsible for extending the serum half-life of antibodies via engagement with the neonatal Fc receptor (FcRn), promoting recycling rather than degradation of these long-lived serum proteins (Figure A). , FcRn also binds albumin in a similar way (but at an orthogonal binding site) (Figure B). When IgG or albumin is taken up by polarized epithelial or endothelial cells, they are packaged into endosomes, which acidify as they traffic through the cell . In this low-pH environment, histidines on albumin and the IgG Fc domain are protonated and binding to FcRn and its cognate light-chain β2 microglobulin (β2m) is enabled .…”