Fc Receptors pp 249-272 | Cite as

FcRn: From Molecular Interactions to Regulation of IgG Pharmacokinetics and Functions

  • Dilip K. Challa
  • Ramraj Velmurugan
  • Raimund J. Ober
  • E. Sally Ward
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 382)


The neonatal Fc receptor, FcRn, is related to MHC class I with respect to its structure and association with β2microglobulin (β2m). However, by contrast with MHC class I molecules, FcRn does not bind to peptides, but interacts with the Fc portion of IgGs and belongs to the Fc receptor family. Unlike the ‘classical’ Fc receptors, however, the primary functions of FcRn include salvage of IgG (and albumin) from lysosomal degradation through the recycling and transcytosis of IgG within cells. The characteristic feature of FcRn is pH-dependent binding to IgG, with relatively strong binding at acidic pH (<6.5) and negligible binding at physiological pH (7.3–7.4). FcRn is expressed in many different cell types, and endothelial and hematopoietic cells are the dominant cell types involved in IgG homeostasis in vivo. FcRn also delivers IgG across cellular barriers to sites of pathogen encounter and consequently plays a role in protection against infections, in addition to regulating renal filtration and immune complex-mediated antigen presentation. Further, FcRn has been targeted to develop both IgGs with extended half-lives and FcRn inhibitors that can lower endogenous antibody levels. These approaches have implications for the development of longer lived therapeutics and the removal of pathogenic or deleterious antibodies.



Antigen presenting cells


Blood–brain barrier


Central nervous system


Dendritic cells


Endothelial cells


Neonatal Fc receptor


Glomerular basement membrane


Hematopoietic cells


Human immunodeficiency virus


Herpes simplex virus


Immune complexes




Intravenous immunoglobulin




Lamina propria


Monoclonal antibodies


Mucosa-associated lymphoid tissue


Major histocompatibility


Mesenteric lymph nodes

Myo Vb

Motor myosin Vb




Proximal convoluted tubule




Transport carrier


Toll-like receptor




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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Dilip K. Challa
    • 1
  • Ramraj Velmurugan
    • 1
  • Raimund J. Ober
    • 1
    • 2
  • E. Sally Ward
    • 1
  1. 1.Department of ImmunologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Department of Electrical EngineeringUniversity of Texas at DallasRichardsonUSA

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