The MHC class I-like IgG receptor controls perinatal IgG transport, IgG homeostasis, and fate of IgG-Fc-coupled drugs.
Abs of the IgG isotype are efficiently transported from mother to neonate and have an extended serum t(1/2) compared with Abs of other isotypes. Circumstantial evidence suggests that the MHC class I-related protein, the neonatal FcR (FcRn), is the FcR responsible for both in vivo functions. To understand the phenotypes imposed by FcRn, we produced and analyzed mice with a defective FcRn gene. The results provide direct evidence that perinatal IgG transport and protection of IgG from catabolism are mediated by FcRn, and that the latter function is key to IgG homeostasis, essential for generating a potent IgG response to foreign Ags, and the basis of enhanced efficacy of Fc-IgG-based therapeutics. FcRn is therefore a promising therapeutic target for enhancing protective humoral immunity, treating autoimmune disease, and improving drug efficacy.
Roopenian
Derry C
DC
The Jackson Laboratory, Bar Harbor, ME 04609, USA. dcr@jax.org
Christianson
Gregory J
GJ
Sproule
Thomas J
TJ
Brown
Aaron C
AC
Akilesh
Shreeram
S
Jung
Nadja
N
Petkova
Stefka
S
Avanessian
Lia
L
Choi
Eun Young
EY
Shaffer
Daniel J
DJ
Eden
Peter A
PA
Anderson
Clark L
CL
D000069594:Abatacept; D000818:Animals; D000831:Animals, Newborn / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D023201:CD40 Ligand / Q000276:immunology*; D003433:Crosses, Genetic; D005260:Female; D006207:Half-Life; D015395:Histocompatibility Antigens Class I / Q000502:physiology*; D006706:Homeostasis / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000008:administration & dosage / Q000378:metabolism*; D007111:Immunity, Cellular / Q000235:genetics; D018796:Immunoconjugates / Q000008:administration & dosage / Q000378:metabolism*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000378:metabolism; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D021381:Protein Transport / Q000235:genetics / Q000276:immunology; D011961:Receptors, Fc / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017452:Receptors, IgG / Q000502:physiology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
D015395:Histocompatibility Antigens Class I; D007106:Immune Sera; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011961:Receptors, Fc; D017452:Receptors, IgG; D014157:Transcription Factors; D023201:CD40 Ligand; D000069594:Abatacept; C100688:Fc receptor, neonatal