Identity of the elusive IgM Fc receptor (FcmuR) in humans.

Identity of the elusive IgM Fc receptor (FcmuR) in humans.
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DOI:
10.1084/jem.20091107
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发表时间:
2009-11-23
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Wang JY
Wang JY
中科院分区:
其他
文献类型:
--
作者:
Kubagawa H;Oka S;Kubagawa Y;Torii I;Takayama E;Kang DW;Gartland GL;Bertoli LF;Mori H;Takatsu H;Kitamura T;Ohno H;Wang JY

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尽管转换免疫球蛋白(IG)同种型的Fc受体(FcR)已被广泛表征,但IgM的FcR(FcμR)仍无法鉴定。通过逆转录病毒表达和功能性克隆,我们在人B系cDNA文库中发现了一个编码真正FcμR的互补DNA(cDNA)。FcμR是一种分子量约为60 kD的跨膜唾液酸糖蛋白,含有一个与其他两种IgM结合受体(多聚体IG受体和Fcα/μR)同源的胞外Ig样结构域,但表现出排他性的Fcμ结合特异性。FcμR的胞质尾区含有保守的Ser和Tyr残基,但没有一个Tyr残基与基于免疫受体酪氨酸的激活、抑制或开关基序匹配。与其他FcR不同,表达FcμR的主要细胞类型是适应性免疫细胞,包括B和T淋巴细胞。在抗原受体连接或佛波酯刺激后,B细胞上的FcμR表达上调,但T细胞上的FcμR表达下调,表明在B和T细胞活化期间FcμR表达的差异调节。尽管该受体最初被命名为Fas凋亡抑制分子3(TOSO),但我们的研究结果表明,FcμR本身在Fas介导的凋亡中没有抑制活性,并且只有当IgM而不是IgG同种型的抗Fas抗体用于诱导凋亡时才能实现这种抑制。
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 Fcα/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.
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