Bredius R G, Fijen C A, De Haas M, Kuijper E J, Weening R S, Van de Winkel J G, Out T A
Clinical and Laboratory Immunology Unit, University of Amsterdam, The Netherlands.
Immunology. 1994 Dec;83(4):624-30.
The four subclasses of IgG have different biological activities associated with their Fc regions. Fc gamma receptors on leucocytes (Fc gamma R) mediate binding and phagocytosis of opsonized particles. Two structurally and functionally distinct allelic polymorphisms of the Fc gamma R have been defined: the H/R131 forms of Fc gamma RIIa (CD32), and the neutrophil antigen 1 (NA1)/NA2 forms of Fc gamma RIIIb (CD16). In this study the activities of allotypes of CD16 are analysed with antibacterial IgG subclass antibodies and with IgG1 and IgG3 anti-Rhesus D, and the activities of CD32 with IgG1 and IgG3 anti-Rhesus D. With respect to the allotypes of CD16, polymorphonuclear leucocytes (PMN) homozygous for Fc gamma RIIb-NA2 exhibited a lower (21-25%) IgG1-mediated phagocytosis of Staphylococcus aureus strain Wood (STAW), Haemophilus influenzae type b (Hib), and Neisseria meningitidis group B (NMen) than IIIb-NA1 PMN. The difference was apparent only when the micro-organisms were opsonized in the absence of complement, and was furthermore enhanced (34-52%) upon blockade of Fc gamma RIIa. In addition, monoclonal IgG3 anti-D-mediated rosette formation and phagocytosis was consistently found to be lower (16%) with Fc gamma RIIIb-NA2 than with IIIb-NA1 PMN. For the allotypes of CD32 we now show that IgG3 anti-D sensitized erythrocytes formed more (50%) rosettes and were phagocytosed at a higher rate with PMN carrying Fc gamma RIIa-H131 than with PMN carrying IIa-R131. Heterozygous Fc gamma RIIa-H/R131 PMN exhibited intermediate phagocytic activity in this respect. This study illustrates a critical role of Fc gamma R allotypes in functional interactions with biologically relevant IgG subclass antibodies.
IgG的四个亚类具有与其Fc区域相关的不同生物学活性。白细胞上的Fcγ受体（FcγR）介导调理素化颗粒的结合和吞噬作用。已确定FcγR的两种结构和功能不同的等位基因多态性：FcγRIIa（CD32）的H/R131形式，以及FcγRIIIb（CD16）的中性粒细胞抗原1（NA1）/NA2形式。在本研究中，用抗菌IgG亚类抗体以及IgG1和IgG3抗恒河猴D分析了CD16同种异型的活性，并用IgG1和IgG3抗恒河猴D分析了CD32的活性。关于CD16的同种异型，FcγRIIb-NA2纯合的多形核白细胞（PMN）对金黄色葡萄球菌伍德菌株（STAW）、b型流感嗜血杆菌（Hib）和B群脑膜炎奈瑟菌（NMen）的IgG1介导的吞噬作用比IIIb-NA1 PMN低（21%-25%）。只有当微生物在无补体的情况下被调理时，这种差异才明显，并且在阻断FcγRIIa后进一步增强（34%-52%）。此外，一致发现，与FcγRIIIb-NA1 PMN相比，FcγRIIIb-NA2的单克隆IgG3抗D介导的玫瑰花结形成和吞噬作用始终较低（16%）。对于CD32的同种异型，我们现在表明，与携带FcγRIIa-H131的PMN相比，IgG3抗D致敏的红细胞与携带FcγRIIa-H131的PMN形成更多（50%）玫瑰花结，并且吞噬率更高。杂合的FcγRIIa-H/R131 PMN在这方面表现出中等吞噬活性。这项研究说明了FcγR同种异型在与生物学相关的IgG亚类抗体的功能相互作用中的关键作用。
