International Immunology, Vol. 15, No. 2, pp. 187-195,
February 2003
© 2003 Japanese Society for Immunology
Evidence to support the cellular mechanism involved in serum IgG homeostasis in humans
1 Center for Immunology and 2 Cancer Immunobiology Center, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Dallas, TX 75390-8576, USA
Correspondence to: E. S. Ward; E-mail: sally.ward{at}UTSouthwestern.edu
Transmitting editor: D. Fearon
IgG is the most abundant serum antibody and is an essential component of the humoral immune response. It is known that the ‘neonatal’ Fc receptor (FcRn) plays a role in maintaining constant serum IgG levels by acting as a protective receptor which binds and salvages IgG from degradation. However, the cellular mechanism that is involved in serum IgG homeostasis is poorly understood. In the current study we address this issue by analyzing the intracellular fate in human endothelial cells of IgG molecules which bind with different affinities to FcRn. The studies show that IgG which do not bind to FcRn accumulate in the lysosomal pathway, providing a cellular explanation for short serum persistence of such antibodies. We have also investigated the saturability of the homeostatic system and find that it has limited capacity. Our observations have direct relevance to the understanding and treatment of IgG deficiency, and to the effective application of therapeutic antibodies.
Keywords: FcRn, human IgG1, immunodeficiency, lysosomal trafficking, serum persistence
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