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CORRESPONDENCE Hiromi Kubagawa: hiromikubagawa{at}uab.edu
Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcµR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcµR in human B-lineage cDNA libraries. FcµR is defined as a transmembrane sialoglycoprotein of
60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fc
/µR) but exhibits an exclusive Fcµ-binding specificity. The cytoplasmic tail of FcµR contains conserved Ser and Tyr residues, but none of the Tyr residues match the immunoreceptor tyrosine-based activation, inhibitory, or switch motifs. Unlike other FcRs, the major cell types expressing FcµR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcµR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcµR expression during B and T cell activation. Although this receptor was initially designated as Fas apoptotic inhibitory molecule 3, or TOSO, our results indicate that FcµR per se has no inhibitory activity in Fas-mediated apoptosis and that such inhibition is only achieved when anti-Fas antibody of an IgM but not IgG isotype is used for inducing apoptosis.
Abbreviations used: 7-AAD, 7-aminoactinomycin D; APC, allophycocyanin; CLL, chronic lymphocytic leukemia; FAIM3, Fas apoptotic inhibitory molecule 3; FcR, Fc receptor; GPI, glycosylphosphatidylinositol; HRP, horseradish peroxidase; MFI, mean fluorescence intensity; MNC, mononuclear cell; pI, isoelectric point; pIgR, polymeric Ig receptor; PKC, protein kinase C; PLC, phospholipase C; SA, streptavidin.
© 2009 Kubagawa et al.
This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
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