Antibodies play an important role in the innate immune system by circulating in the bloodstream to fight off invading pathogens. IgG is the most prevalent of the five classes of antibodies (IgA, IgD, IgE, IgG, and IgM) and is the only one transmitted from a mother to her offspring. IgG is transported across the epithelium of the placenta by the neonatal Fc receptor (FcRn) (1). FcRn is a 40 kDa protein encoded by the FCGRT gene. FcRn binds to the Fc domain of IgG and transports the antibody in a pH dependent mechanism. Outside of the neonatal period, FcRn continues to play a role in IgG regulation. FcRn binds to IgG in the serum to prolong the half-life of this immunoprotective antibody. It has also been suggested that FcRn binds to albumin and serves the same protective purpose (2). Modification of the FcRn-IgG interaction is being studied as a strategy to increase the lifespan of therapeutic antibodies or to shorten the lifespan of pathogenic antibodies, such as those implicated in autoimmune diseases.
Gupta et. al. used the FcRn antibody to discover that FcRn facilitates HIV-1 transmission at mucosal surfaces (3). The group used the FcRn antibody to assess expression of FcRn in genital mucosal tissue sections, where they found an enrichment of FcRn in areas of columnar epithelia. They also used the FcRn antibody to confirm FcRn knockdowns and then compared the HIV-1 infection rate of these cells to their controls. The group found remarkably diminished levels of infection in the FcRn knockdowns, indicating a role for FcRn in HIV-1 transcytosis. Meanwhile, infection of the control cells was pH dependent, a well characterized property of FcRn transport.
Meanwhile, Morel et. al. used the FcRn antibody to determine if FcRn played a role in the neutralization of hepatitis C virus (HCV) as it does in influenza A neutralization (4). The group used the FcRn antibody to confirm FcRn knockdowns in hepatocytes. Then they compared HCV neutralization in the knockdowns to their controls and didn’t find a significant difference, suggesting other mechanisms for this process.
Novus Biologicals offers FCRN/FCGRT reagents for your research needs including:
PMIDs