title: Electron tomography of late stages of FcRn-mediated antibody transcytosis in neonatal rat small intestine.
abstract: The neonatal Fc receptor (FcRn) transports maternal immunoglobulin (IgG) across epithelia to confer passive immunity to mammalian young. In newborn rodents, FcRn transcytoses IgG from ingested milk across the intestinal epithelium for release into the bloodstream. We used electron tomography to examine FcRn transport of Nanogold-labeled Fc (Au-Fc) in neonatal rat jejunum, focusing on later aspects of transport by chasing Au-Fc before fixation. We observed pools of Au-Fc in dilated regions of the lateral intercellular space (LIS), likely representing exit sites where Au-Fc accumulates en route to the blood. Before weaning, the jejunum functions primarily in IgG transport and exhibits unusual properties: clathrin-rich regions near/at the basolateral LIS and multivesicular bodies (MVBs) expressing early endosomal markers. To address whether these features are related to IgG transport, we examined LIS and endocytic/transcytotic structures from neonatal and weaned animals. Weaned samples showed less LIS-associated clathrin. MVBs labeled with late endosomal/lysosomal markers were smaller than their neonatal counterparts but contained 10 times more internal compartments. These results are consistent with hypotheses that clathrin-rich basolateral regions in neonatal jejunum are involved in IgG exocytosis and that MVBs function in IgG transport while FcRn is expressed but switch to degradative functions after weaning, when the jejunum does not express FcRn or transport IgG.
authors.affiliation: Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Ladinsky
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Huey-Tubman
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Bjorkman
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D022163:Clathrin-Coated Vesicles / Q000378:metabolism / Q000648:ultrastructure; D055032:Electron Microscope Tomography; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007082:Ileum / Q000378:metabolism* / Q000648:ultrastructure; D007074:Immunoglobulin G / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000648:ultrastructure; D007583:Jejunum / Q000378:metabolism* / Q000648:ultrastructure; D051907:Lysosomal Membrane Proteins / Q000378:metabolism; D057146:Multivesicular Bodies / Q000378:metabolism / Q000648:ultrastructure; D021381:Protein Transport; D051381:Rats; D011961:Receptors, Fc / Q000378:metabolism*; D057900:Transcytosis; D014886:Weaning; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism; D052118:Lysosomal-Associated Membrane Protein 1
chemical_list: D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D051907:Lysosomal Membrane Proteins; D011961:Receptors, Fc; D020696:rab5 GTP-Binding Proteins; C489117:Lamp1 protein, rat; D052118:Lysosomal-Associated Membrane Protein 1; C100688:Fc receptor, neonatal