| The neonatal Fc-receptor for IgG (FcRn) has two well characterized functions. The first function is mediating the transfer of passive humoral immunity from the mother to the newborn. The second function is extending the serum half-life of IgG in the adult. In the adult, the main site for FcRn function is thought to be the vascular endothelium where FcRn returns internalized IgG back into the circulation and prevents it from being degraded in the lysosome. However, previous studies have shown that FcRn is expressed in different tissues and the function, if any, of FcRn at these extravascular sites is unknown. Using FcRn knockout mice as a specificity control, we documented the expression pattern of FcRn across a range of tissues. We were able to both confirm previous reports and document expression of FcRn in tissues not examined previously. Strikingly, FcRn is highly expressed in antigen presenting cells (APCs) in several organs where it contributed significantly to extending the serum half-life of IgG. This finding suggests that both vascular endothelial cells and bone-marrow derived cells protect serum IgG from catabolism.;We observed that upon administration of exogenous protein, mice accumulate protein in the glomeruli of their kidneys in an age- and dose-dependent manner. We hypothesized that specific receptors expressed in the glomerular epithelial cell (podocyte) mediated clearance of protein from the glomerular filter. Consistent with this idea, we detected FcRn in podocytes which form the final barrier to filtration. FcRn was at least partially responsible for the removal of proteins deposited at the kidney filter. These findings revise our understanding of the principles of glomerular filtration and suggest that defects in the endocytic machinery of the podocyte can lead to kidney disease. |
