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)

Abstract

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.

Abbreviations

APCs

Antigen presenting cells

BBB

Blood–brain barrier

CNS

Central nervous system

DCs

Dendritic cells

ECs

Endothelial cells

FcRn

Neonatal Fc receptor

GBM

Glomerular basement membrane

HCs

Hematopoietic cells

HIV

Human immunodeficiency virus

HSV

Herpes simplex virus

ICs

Immune complexes

Ig

Immunoglobulin

IVIG

Intravenous immunoglobulin

KO

Knockout

LP

Lamina propria

mAbs

Monoclonal antibodies

MALT

Mucosa-associated lymphoid tissue

MHC

Major histocompatibility

MLNs

Mesenteric lymph nodes

Myo Vb

Motor myosin Vb

OVA

Ovalbumin

PCT

Proximal convoluted tubule

β2m

β2microglobulin

TC

Transport carrier

TLR

Toll-like receptor

WT

Wildtype

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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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