ROLE OF NEUTROPHIL FC-GAMMA-RIIA (CD32) AND FC-GAMMA-RIIIB (CD16) POLYMORPHIC FORMS IN PHAGOCYTOSIS OF HUMAN IGG1-OPSONIZED AND IGG3-OPSONIZED BACTERIA AND ERYTHROCYTES

The four subclasses ofIgG have different biological activities associa ted with their Fc regions. Fc gamma receptors on leucocytes (Fc gamma R) mediate binding and phagocytosis of opsonized particles. Two struct urally and functionally distinct allelic polymorphisms of the Fc gamma R have been defined: the H/R131 forms of Fc gamma RIIa (CD32), and th e neutrophil antigen 1 (NA1)/NA2 forms of Fc gamma RIIIb (CD16). In th is study the activities of allotypes of CD16 are analysed with antibac terial IgG subclass antibodies and with IgG1 and IgG3 anti-Rhesus D, a nd the activities of CD32 with IgG1 and IgG3 anti-Rhesus D. With respe ct to the allotypes of CD16, polymorphonuclear leucocytes (PMN) homozy gous for Fc gamma RIIIb-NA2 exhibited a lower (21-25%) IgG1-mediated p hagocytosis of Staphylococcus aureus strain Wood (STAW), Haemophilus i nfluenzae type b (Hib), and Neisseria meningitidis group B (NMen) than IIIb-NA1 PMN. The difference was apparent only when the micro-organis ms were opsonized in the absence of complement, and was furthermore en hanced (34-52%) upon blockade of Fc gamma RIIa. In addition, monoclona l IgG3 anti-D-mediated rosette formation and phagocytosis was consiste ntly found to be lower (16%) with Fc gamma RIIIb-NA2 than with IIIb-NA 1 PMN. For the allotypes of CD32 we now show that IgG3 anti-D sensitiz ed erythrocytes formed more (50%) rosettes and were phagocytosed at a higher rate with PMN carrying Fc gamma RIIa-H131 than with PMN carryin g IIa-R131. Heterozygous Fc gamma RIIa-H/R131 PMN exhibited intermedia te phagocytic activity in this respect. This study illustrates a criti cal role of Fc gamma R allotypes in functional interactions with biolo gically relevant IgG subclass antibodies.