Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene.
Expression of functional CD32 molecules on human NK cells is determined by an allelic polymorphism of the FcgammaRIIC gene.
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DOI：
10.1182/blood.v91.7.2369
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发表时间：
1998-04
期刊：
影响因子：
20.3
通讯作者：
Diana Metes;Linda K. Ernst;William H. Chambers;A. Sulica;Ronald B. Herberman;P. A. Morel
中科院分区：
文献类型：
--
作者：
Diana Metes;Linda K. Ernst;William H. Chambers;A. Sulica;Ronald B. Herberman;P. A. Morel
人类自然杀伤（NK）细胞被认为仅表达Fc γ RIIIA（CD 16），但最近的报告表明，NK细胞还表达第二种类型的Fc γ R，即Fc γ RII（CD 32）。我们已经分离、克隆和测序了来自几个正常个体的NK细胞的FcgammaRII的全长cDNA，其可能代表FcgammaRIIC基因的四种不同产物。一种转录物（IIc 1）与已经描述的Fc γ RIIc形式相同。其他三个（IIc 2-IIc 4）似乎代表同一基因的独特的选择性剪接产物，并且包括可能的可溶形式。全长克隆的分析揭示了第一胞外外显子的等位基因多态性，导致功能性开放阅读框同种型或无效等位基因。稳定转染实验使我们能够确定抗CD 32单克隆抗体与Fc γ RIIc的独特结合模式。NK细胞制备物的进一步分析揭示了CD 32表达的异质性，范围从缺乏CD 32表达的供体到表达能够触发细胞毒性的高水平CD 32的供体。表达差异与无效等位基因的存在或不存在相关。这些数据显示某些个体在其NK细胞上表达高水平的功能性Fc γ RIIc同种型。
Human natural killer (NK) cells were thought to express only FcgammaRIIIA (CD16), but recent reports have indicated that NK cells also express a second type of FcgammaR, ie, FcgammaRII (CD32). We have isolated, cloned, and sequenced full-length cDNAs of FcgammaRII from NK cells derived from several normal individuals that may represent four different products of the FcgammaRIIC gene. One transcript (IIc1) is identical with the already described FcgammaRIIc form. The other three (IIc2-IIc4) appear to represent unique, alternatively spliced products of the same gene, and include a possible soluble form. Analyses of the full-length clones have revealed an allelic polymorphism in the first extracellular exon, resulting in either a functional open reading frame isoform or a null allele. Stable transfection experiments enabled us to determine a unique binding pattern of anti-CD32 monoclonal antibodies to FcgammaRIIc. Further analyses of NK-cell preparations revealed heterogeneity in CD32 expression, ranging from donors lacking CD32 expression to donors expressing high levels of CD32 that were capable of triggering cytotoxicity. Differences in expression were correlated with the presence or absence of null alleles. These data show that certain individuals express high levels of functional FcgammaRIIc isoforms on their NK cells.