Crucial role of Fc gamma RIIa (CD32) in assessment of functional anti-Streptococcus pneumoniae antibody activity in human sera

Immunoglobulin G (IgG)-mediated phagocytosis by polymorphonuclear leukocyte s (PMNL) constitutes the main defense against Streptococcus pneumoniae, Two leukocyte IgG receptors, Fc gamma RIIa and Fc gamma RIIIb, are constitutiv ely expressed on PMNL. Blocking experiments showed Fc gamma RIIa is crucial for opsonophagocytosis of serum-opsonized S. pneumoniae. The biallelic, ge netically determined Fc gamma RIIa polymorphism (Fc gamma RIIa-R131 vs. IIa -H131) determines the capacity of IgG2-mediated phagocytosis via this recep tor. Comparative studies with PMNL from donors either homozygous for Fc gam ma RIIa-R131 or IIa-H131 showed the latter had higher phagocytic capacity. These results were confirmed in Fc gamma RIIa-R131- and Fc gamma RIIa-H131- transfected IIA1.6 cells. The performance of Fc gamma RIIa-transfected cell s in S. pneumoniae phagocytosis was validated using sera from adults and ch ildren. Serum-induced phagocytic activity depended mainly on anti-pneumococ cal IgG2 antibodies. Results obtained with PMNL and IIA1.6 cells showed hig h correlation (r = 0.94; P < .001), and support that Fc gamma RIIa transfec tants are a good alternative to PMNL as effector cells in opsonophagocytosi s assays.