ON THE INTERACTION OF IGG SUBCLASSES WITH THE LOW AFFINITY FC-GAMMA-RIIA (CD32) ON HUMAN MONOCYTES, NEUTROPHILS, AND PLATELETS - ANALYSIS OF A FUNCTIONAL POLYMORPHISM TO HUMAN IGG2
ON THE INTERACTION OF IGG SUBCLASSES WITH THE LOW AFFINITY FC-GAMMA-RIIA (CD32) ON HUMAN MONOCYTES, NEUTROPHILS, AND PLATELETS - ANALYSIS OF A FUNCTIONAL POLYMORPHISM TO HUMAN IGG2
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DOI：
10.1172/jci116022
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发表时间：
1992-10-01
影响因子：
15.9
通讯作者：
VANDEWINKEL, JGJ
中科院分区：
文献类型：
--
作者：
PARREN, PWHI;WARMERDAM, PAM;VANDEWINKEL, JGJ
低亲和力IgG Fc受体Fc γ RIIa（CD32）的同种异型形式，由于其与小鼠（m）IgG 1的弱反应性而被称为低应答者（LR），与人（h）IgG 2有效相互作用。Fc γ RIIa（LR）是第一个已知的结合该IgG亚类的人FcR。在这项研究中，我们分析了Fc γ RIIa在稳定的hIgG亚类二聚体结合中的作用，以及在使用嵌合抗CD3 mAb诱导T细胞有丝分裂中的作用。我们证明了hIgG2的功能多态性在大多数FcgammaR外周血细胞（单核细胞、中性粒细胞和血小板）上表达。我们能够评估Fc γ RII介导的IgG结合，而不干扰其他Fc γ R类，通过阻断单核细胞上的Fc γ RI，并通过使用缺乏Fc γ RIIIB基因的个体的中性粒细胞。该研究表明，对于Fc γ RIIa（LR），hIgG3 > hIgG1，hIgG2远大于hIgG4，对于Fc γ RIIa（HR），hIgG3，hIgG1远大于hIgG2 > hIgG4。比较两种Fc γ RIIa同种异型形式纯合个体的血清hIgG水平，我们观察到表达hIgG 2结合LR同种异型形式的个体中hIgG 2血清水平显著较低。该观察结果可能暗示Fc γ RIIa调节人中hIgG亚类的产生或周转。
An allotypic form of the low affinity IgG Fc receptor FcgammaRIIa (CD32), termed low responder (LR) because of its weak reactivity with mouse (m) IgG1, interacts efficiently with human (h) IgG2. FcgammaRIIa(LR) is the first known human FcR that binds this IgG subclass. In this study, we analyzed the role of FcgammaRIIa in binding of stable hIgG-subclass dimers, and in induction of T cell mitogenesis using chimeric anti-CD3 mAb. We demonstrate that the functional polymorphism to hIgG2 is expressed on the majority of FcgammaR-bearing peripheral blood cells: monocytes, neutrophils, and platelets. We were able to assess FcgammaRII-mediated IgG-binding without interference of other FcgammaR-classes, by blockade of FcgammaRI on monocytes, and by using neutrophils of an individual deficient for the FcgammaRIIIB gene. This study indicates as subclass specificity: hIgG3 > hIgG1,hIgG2 much greater than hIgG4 for FcgammaRIIa(LR) and hIgG3,hIgG1 much greater than hIgG2 > hIgG4 for FcgammaRIIa(HR). Comparing the serum hIgG levels of individuals homozygous for the two FcgammaRIIa allotypic forms, we observed significantly lower hIgG2 serum levels in individuals expressing the hIgG2-binding LR allotypic form. This observation may implicate that FcyRIIa regulates hIgG subclass production or turnover in man.