title: Identification of the transferrin receptor as a novel immunoglobulin (Ig)A1 receptor and its enhanced expression on mesangial cells in IgA nephropathy.
abstract: The biological functions of immunoglobulin (Ig)A antibodies depend primarily on their interaction with cell surface receptors. Four IgA receptors are presently characterized. The FcalphaRI (CD89) expressed by myeloid cells selectively binds IgA1 and IgA2 antibodies, whereas the poly-IgR, Fcalpha/muR, and asialoglycoprotein receptors bind other ligands in addition to IgA. IgA binding by mesangial cells, epithelial cells, and proliferating lymphocytes is also well documented, but the nature of the IgA receptors on these cells remains elusive. A monoclonal antibody (A24) is described here that specifically blocks IgA binding to epithelial and B lymphocyte cell lines. Both the A24 antibody and IgA1 myelomas bind a cell surface protein that is identified as the transferrin receptor (CD71). The transferrin receptor selectively binds IgA1 antibodies, monomeric better than polymeric forms, and the IgA1 binding is inhibitable by transferrin. Transferrin receptor expression is upregulated on cultured mesangial cells as well as on glomerular mesangial cells in patients with IgA nephropathy. The characterization of transferrin receptor as a novel IgA1 receptor on renal mesangial cells suggests its potential involvement in the pathogenesis of IgA nephropathy.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U25, Necker Hospital, Paris 75743 Cédex 15, France.
authors.forename: I C
authors.initials: IC
authors.lastname: Moura
authors.forename: M N
authors.initials: MN
authors.lastname: Centelles
authors.forename: M
authors.initials: M
authors.lastname: Arcos-Fajardo
authors.forename: D M
authors.initials: DM
authors.lastname: Malheiros
authors.forename: J F
authors.initials: JF
authors.lastname: Collawn
authors.forename: M D
authors.initials: MD
authors.lastname: Cooper
authors.forename: R C
authors.initials: RC
authors.lastname: Monteiro
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000378:metabolism*; D005922:Glomerulonephritis, IGA / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D011961:Receptors, Fc / Q000378:metabolism*; D011990:Receptors, Transferrin / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000911:Antibodies, Monoclonal; C045281:IgA receptor; D011961:Receptors, Fc; D011990:Receptors, Transferrin