FcRn: The Architect Behind the Immune and Nonimmune Functions of IgG and Albumin.
The neonatal FcR (FcRn) belongs to the extensive and functionally divergent family of MHC molecules. Contrary to classical MHC family members, FcRn possesses little diversity and is unable to present Ags. Instead, through its capacity to bind IgG and albumin with high affinity at low pH, it regulates the serum half-lives of both of these proteins. In addition, FcRn plays an important role in immunity at mucosal and systemic sites through its ability to affect the lifespan of IgG, as well as its participation in innate and adaptive immune responses. Although the details of its biology are still emerging, the ability of FcRn to rescue albumin and IgG from early degradation represents an attractive approach to alter the plasma half-life of pharmaceuticals. We review some of the most novel aspects of FcRn biology, immune as well as nonimmune, and provide some examples of FcRn-based therapies.
Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115; Department of Medicine, Harvard Medical School, Boston, MA 02115;
Michal
M
Pyzik
Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115; Department of Medicine, Harvard Medical School, Boston, MA 02115; Division of Gastroenterology, Department of Medicine, Erlangen University Hospital, Friedrich Alexander University Erlangen-Nueremberg, 91054 Erlangen, Germany;
Timo
T
Rath
Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA 02115; Harvard Digestive Diseases Center, Boston, MA 02115; and Department of Pediatrics, Harvard Medical School, Boston, MA 02115.
Wayne I
WI
Lencer
Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115; Department of Medicine, Harvard Medical School, Boston, MA 02115;
Kristi
K
Baker
Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115; Department of Medicine, Harvard Medical School, Boston, MA 02115; Harvard Digestive Diseases Center, Boston, MA 02115; and rblumberg@partners.org.
Richard S
RS
Blumberg
D000418:Albumins / Q000276:immunology*; D000818:Animals; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D007074:Immunoglobulin G / Q000276:immunology*; D011961:Receptors, Fc / Q000276:immunology*
D000418:Albumins; D015395:Histocompatibility Antigens Class I; D007074:Immunoglobulin G; D011961:Receptors, Fc; C100688:Fc receptor, neonatal