Identity of the elusive IgM Fc receptor (FcμR) in humans

Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (Fc mu R) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide Fc mu R in human B-lineage cDNA libraries. Fc mu R is defined as a transmembrane sialoglycoprotein of similar to 60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fc alpha/mu R) but exhibits an exclusive Fc mu-binding specificity. The cytoplasmic tail of Fc mu R 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 Fc mu R are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, Fc mu R expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of Fc mu R 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 Fc mu R 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.