Journal
INTERNATIONAL IMMUNOLOGY
Volume 15, Issue 2, Pages 187-195Publisher
OXFORD UNIV PRESS
DOI: 10.1093/intimm/dxg018
Keywords
FcRn; human IgG1; immunodeficiency; lysosomal trafficking; serum persistence
Categories
Funding
- NIAID NIH HHS [R01 AI050747, R01 AI039167, R01 AI/RR 50747, R01 AI 39167] Funding Source: Medline
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available