title: Unique ligand-binding property of the human IgM Fc receptor.
abstract: The IgM Fc receptor (FcμR) is the newest FcR, and coligation of FcμR and Fas/CD95 on Jurkat cells with agonistic IgM anti-Fas mAb was shown to inhibit Fas-induced apoptosis. The ligand-binding activity of human FcμR was further examined. FcμR-mediated protection from apoptosis was partially blocked by addition of 10(4) molar excess of IgM or its soluble immune complexes, but it could be inhibited by addition of 10-fold excess of IgM anti-CD2 mAb. This suggests that FcμR binds more efficiently to the Fc portion of IgM reactive with plasma-membrane proteins than to the Fc portion of IgM in solution. The former interaction occurred in cis on the same cell surface, but not in trans between neighboring cells. This cis engagement of FcμR resulted in modulation of Ca(2+) mobilization via CD2 on Jurkat cells or BCRs on blood B cells upon cross-linkage with the corresponding IgM mAbs. Several functional changes were observed with FcμR mutants: 1) significant increase in IgM ligand binding in the cytoplasmic tail-deletion mutant, 2) enhanced cap formation in FcμR upon IgM binding at 4°C with a point mutation of the transmembrane His to Phe, and 3) less protective activity of FcμR in IgM anti-Fas mAb-mediated apoptosis assays with a point mutation of the membrane-proximal Tyr to Phe. These findings show the importance of the cis engagement of FcμR and its critical role in receptor function. Hence, FcμR on B, T, and NK cells may modulate the function of surface proteins recognized by natural or immune IgM Abs on the shared membrane cell surface.
authors.affiliation: Division of Laboratory Medicine, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; and.
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Honjo
authors.affiliation: Division of Laboratory Medicine, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; and.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kubagawa
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294.
authors.forename: John F
authors.initials: JF
authors.lastname: Kearney
authors.affiliation: Division of Laboratory Medicine, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294; and hiromikubagawa@uab.edu.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kubagawa
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002460:Cell Line; D005455:Fluorescent Antibody Technique; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000276:immunology*; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016297:Mutagenesis, Site-Directed; D011961:Receptors, Fc / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D000936:Antigen-Antibody Complex; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D011961:Receptors, Fc; C035311:immunoglobulin M receptor