Neutrophil responsiveness to IgG, as determined by fixed ratios of mRNA levels for activating and inhibitory FcγRII (CD32), is stable over time and unaffected by cytokines

Abstract

We tested the hypothesis that the ratio between the activating and inhibitory Fcγ receptor type II (FcγRII) in neutrophils determines their responsiveness to immune complexes. We measured mRNA levels of FcγRII isoforms and observed differences in the ratio of FcγRIIa to FcγRIIb2 mRNA in granulocytes of 50 white and 10 black healthy volunteers, and found 4 discrete groups of ratios (ie, 4:1; 3:1, 2:1, or 1:1). The response to either dimeric IgG or aggregated IgG (aIgG) was assessed. Up-regulation of CD11b on the surface as well as the elastase release was significantly more pronounced in neutrophils with a high FcγRIIa/FcγRIIb2 mRNA ratio of 4:1 compared with a 2:1 or 1:1 ratio. Individual ratios as well as the functional responsiveness of neutrophils were constant over time, as was tested over 12 months. Neutrophil stimulation with various agents in vitro did not alter the FcγRIIa/FcγRIIb2 mRNA ratio in the neutrophils of these donors, in clear contrast to the findings in their mononuclear cells. We found a strong association between the 2B.4 haplotype of the FCGR2B promoter with increased transcriptional activity in individuals with 1:1 ratios and the more common low-expression 2B.1 haplotype in individuals with FcγRIIa/FcγRIIb2 mRNA ratios of 2:1, 3:1, or 4:1.