Identification of the Transferrin Receptor as a Novel Immunoglobulin (Ig)a1 Receptor and Its Enhanced Expression on Mesangial Cells in Iga Nephropathy

doi:10.1084/jem.194.4.417

Published online 20 August 2001. doi:10.1084/jem.194.4.417

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© The Rockefeller University Press, 0022-1007/2001/8/417/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 4, August 20, 2001 417-426

Original Article

Identification of the Transferrin Receptor as a Novel Immunoglobulin (Ig)a1 Receptor and Its Enhanced Expression on Mesangial Cells in Iga Nephropathy

Ivan C. Moura^a, Miguel N. Centelles^a, Michelle Arcos-Fajardo^a, Denise M. Malheiros^b, James F. Collawn^c, Max D. Cooper^d, and Renato C. Monteiro^a

^a Institut National de la Santé et de la Recherche Médicale (INSERM) U25, Necker Hospital, Paris 75743 Cédex 15, France
^b Division of Nephrology, University of São Paulo Medical School, São Paulo 01246, Brazil
^c Department of Cell Biology, University of Alabama at Birmingham, Birmingham, AL 35294
^d The Howard Hughes Medical Institute, University of Alabama at Birmingham, Birmingham, AL 35294
INSERM U25, Hôpital Necker, 161, rue de Sèvres, 75743 Paris Cédex 15, France.33-1-43-06-23-8833-1-44 49-53-66

monteiro{at}necker.fr

The biological functions of immunoglobulin (Ig)A antibodiesdepend primarily on their interaction with cell surface receptors.Four IgA receptors are presently characterized. The Fc ${alpha}$ RI (CD89)expressed by myeloid cells selectively binds IgA1 and IgA2 antibodies,whereas the poly-IgR, Fc ${alpha}$ /µR, and asialoglycoprotein receptorsbind other ligands in addition to IgA. IgA binding by mesangialcells, epithelial cells, and proliferating lymphocytes is alsowell documented, but the nature of the IgA receptors on thesecells remains elusive. A monoclonal antibody (A24) is describedhere that specifically blocks IgA binding to epithelial andB lymphocyte cell lines. Both the A24 antibody and IgA1 myelomasbind a cell surface protein that is identified as the transferrinreceptor (CD71). The transferrin receptor selectively bindsIgA1 antibodies, monomeric better than polymeric forms, andthe IgA1 binding is inhibitable by transferrin. Transferrinreceptor expression is upregulated on cultured mesangial cellsas well as on glomerular mesangial cells in patients with IgAnephropathy. The characterization of transferrin receptor asa novel IgA1 receptor on renal mesangial cells suggests itspotential involvement in the pathogenesis of IgA nephropathy.

Key Words: transferrin receptor • IgA • Fc receptor • mesangial cells • IgA nephropathy

I.C. Moura and M.N. Centelles contributed equally to this work.

Abbreviations used in this paper: CEF, chicken embryo fibroblast;IgAN, IgA nephropathy; SIgA, secretory IgA; TfR, transferrinreceptor.

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