Characterization of the Fc mu receptor on human natural killer cells. Interaction with its physiologic ligand, human normal IgM, specificity of binding, and functional effects.
Characterization of the Fc mu receptor on human natural killer cells. Interaction with its physiologic ligand, human normal IgM, specificity of binding, and functional effects.
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人类自然杀伤细胞上 Fc mu 受体的表征。
DOI：
10.4049/jimmunol.151.6.3018
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发表时间：
1993
影响因子：
4.4
通讯作者：
R. Herberman
中科院分区：
文献类型：
--
作者：
Luminita Pricop;H. Rabinowich;P. A. Morel;A. Sulica;T. Whiteside;R. Herberman
在用人正常IgM处理后，通过粘附于塑料选择的78 +/- 8%的纯化的CD 3-CD 56+静息人NK细胞和93 +/- 6%的IL-2活化的NK细胞与FITC-山羊抗人IgM反应。IgM与人NK细胞上IgM的FcR（Fc mu R）的结合不具有种属特异性，因为小鼠骨髓瘤IgM也与这些细胞结合。与抗CD 16 mAb孵育后结合IgM的CD 56+细胞百分比与单独与培养基孵育的细胞相似（95 +/- 1% vs 93 +/- 4%）。抗CD 16 mAb与NK细胞上Fc γ RIII的结合不受IgM预处理的影响（65 +/- 12% vs 69 +/- 4%）。据报道，CD 7分子是T细胞表面上的Fc μ R。双色流式细胞术显示94 +/- 3%的CD 3-CD 56+静息NK细胞和71 +/- 16%的活化NK细胞为CD 7+。用三种抗CD 7 mAb（Leu-9、8H 8 -1和LAU-A1）预孵育NK细胞未能阻断IgM与Fc mu R的结合。调节CD 7分子脱离细胞表面（CD 7 + = 1.5% +/- 0.3）不会降低IgM结合，因此排除了IgM抗CD 7可能与同一分子的不同表位结合的可能性。这些数据表明，Fc mu R是一种特异性Ig结合结构，不同于Fc γ RIII（CD 16）或CD 7。NK细胞上的Fc mu R起信号转导分子的作用，因为向R-NK细胞中添加0.2 mg/ml IgM导致[Ca 2 +]i快速增加（δ = 40 nM）。通过Fc mu R进行信号传导后的早期事件之一是NK细胞中IFN-γ基因表达和IFN-γ产生的下调。在NK细胞培养过程中IgM的存在一致地降低HLA-DR的表达（16%对对照中的40%）。因此，Fc μ R，人NK细胞上组成型表达的受体，似乎是一种重要的功能分子，其向NK细胞递送负调节信号。
After treatment with human normal IgM, 78 +/- 8% of purified CD3-CD56+ resting human NK cells and 93 +/- 6% of IL-2-activated NK cells selected by adherence to plastic reacted with FITC-goat anti-human IgM. Binding of IgM to the FcR for IgM (Fc mu R) on human NK cells was not species specific because mouse myeloma IgM also bound to these cells. The percentage of CD56+ cells binding IgM after incubation with anti-CD16 mAb was similar to that of cells incubated with medium alone (95 +/- 1% vs 93 +/- 4%). Binding of anti-CD16 mAb to Fc gamma RIII on NK cells was unaffected by pretreatment with IgM (65 +/- 12% vs 69 +/- 4%). The CD7 molecule has been reported to be the Fc mu R on the surface of T cells. Two-color flow cytometry showed that 94 +/- 3% of CD3-CD56+ resting NK cells and 71 +/- 16% of activated NK cells were CD7+. Preincubation of NK cells with three anti-CD7 mAb (Leu-9, 8H8-1, and LAU-A1) failed to block the binding of IgM to the Fc mu R. Modulation of the CD7 molecule off the cell surface (CD7+ = 1.5% +/- 0.3) did not reduce IgM binding, thus excluding the possibility that IgM anti-CD7 might bind to different epitopes of the same molecule. These data indicate that the Fc mu R is a specific Ig-binding structure, distinct from the Fc gamma RIII (CD16) or CD7. The Fc mu R on NK cells functions as a signal-transducing molecule because the addition of 0.2 mg/ml IgM to R-NK cells caused a rapid increase in [Ca2+]i (delta = 40 nM). One of the early events that followed signaling through the Fc mu R was the down-modulation of IFN-gamma gene expression and IFN gamma production in NK cells. The presence of IgM during culture of NK cells consistently decreased the expression of HLA-DR (16% vs 40% in control). Thus, the Fc mu R, a constitutively-expressed receptor on human NK cells, seems to be an important functional molecule, which delivers negative regulatory signals to NK cells.