FcRn recycling pathway.29 IgG and Fc fusion proteins are taken up from circulation into cells by nonspecific pinocytosis and/or endocytosis mechanisms.49 As the endosomes become acidic, the Fc domain of IgG or Fc fusion proteins binds to FcRn. Once the endosome fuses back at the cell surface, Fc dissociates from FcRn at neutral pH and IgG and Fc fusion proteins are released back into the circulation.49 In contrast, circulating proteins that do not interact with FcRn are trafficked to endosomal and lysosomal degradation pathways.29,50 Ultimately, Fc degrades naturally and does not accumulate in the body.51 Despite its name, the expression of human FcRn is stable throughout life.52 Reprinted with permission from Roopenian and Akilesh.29 Copyright 2007, Nature Publishing Group.
