Identity of the elusive IgM Fc receptor (FcmuR) in humans.
Although Fc receptors (FcRs) for switched immunoglobulin (Ig) isotypes have been extensively characterized, FcR for IgM (FcmuR) has defied identification. By retroviral expression and functional cloning, we have identified a complementary DNA (cDNA) encoding a bona fide FcmuR in human B-lineage cDNA libraries. FcmuR is defined as a transmembrane sialoglycoprotein of approximately 60 kD, which contains an extracellular Ig-like domain homologous to two other IgM-binding receptors (polymeric Ig receptor and Fcalpha/muR) but exhibits an exclusive Fcmu-binding specificity. The cytoplasmic tail of FcmuR 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 FcmuR are adaptive immune cells, including B and T lymphocytes. After antigen-receptor ligation or phorbol myristate acetate stimulation, FcmuR expression was up-regulated on B cells but was down-modulated on T cells, suggesting differential regulation of FcmuR 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 FcmuR 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.
Kubagawa
Hiromi
H
Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Oka
Satoshi
S
Kubagawa
Yoshiki
Y
Torii
Ikuko
I
Takayama
Eiji
E
Kang
Dong-Won
DW
Gartland
G Larry
GL
Bertoli
Luigi F
LF
Mori
Hiromi
H
Takatsu
Hiroyuki
H
Kitamura
Toshio
T
Ohno
Hiroshi
H
Wang
Ji-Yang
JY
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002273:Carcinogens / Q000494:pharmacology; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019014:fas Receptor / Q000235:genetics / Q000276:immunology
D051017:Apoptosis Regulatory Proteins; D002273:Carcinogens; D018076:DNA, Complementary; C491901:FAS protein, human; C112037:FCMR protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008565:Membrane Proteins; D011961:Receptors, Fc; D019014:fas Receptor; D013755:Tetradecanoylphorbol Acetate