The spontaneous ability of normal human IgG to inhibit the Fc receptors of normal human monocytes is related to their binding capacity to lectins

The lectin-binding capacity of 96 normal human IgG, assessed by solid-phase
radioimmunoassay, strikingly varied according to the lectin considered. Indeed,
half of the IgG samples exhibited peanut agglutinin (PNA)- and pokeweed
mitogen-specific binding capacities superior or equal to 4%, whereas less than
15% of IgG similarly bound to concanavalin A (Con A) and to phytohemagglutinin.
The ability of those IgG to inhibit the Fc receptor (Fc-R) function of human
monocytes, measured by a classical rosette assay, was inversely correlated to
their binding ratios to PNA and Con A only. By affinity chromatography, three
groups of IgG were separated: the IgG purified on agarose-PNA columns slightly
reduced the Fc-R function (40-45% inhibition); the IgG purified on Sepharose-Con
A columns exhibited the highest inhibitory properties (80-85% inhibition); the
IgG that did not bind to PNA and Con A columns possessed intermediate inhibitory
properties (65-70% inhibition). The different effect of IgG on Fc receptors was
conserved when monocytes were first treated by trypsin and was unrelated to their
specific binding to human monocytes, to their subclasses, and to their C1q- or
protein A-binding capacities. Incubation of monocytes with D-galactose (10 mM)
significantly improved their capacity to form IgG rosettes, whereas their
incubation with D-mannose (10 mM) significantly reduced the Fc-R function.
Scatchard plots of 125I-IgG1 myeloma protein binding to monocytes were linear
under basal conditions, as well as after a prior incubation of the cells with
D-galactose or D-mannose. Monocytes bound about 16,000 molecules of IgG1 per cell
in each instance. In contrast, the mean association constant (Ka) for IgG1
binding was 2.59 +/- 0.50 X 10(8) M-1 under basal conditions, 4.4 +/- 0.75 X
10(8) M-1 after D-galactose incubation, and 1.35 +/- 0.50 X 10(8) M-1 after
D-mannose incubation. These data suggest that the level of human monocyte Fc-R
function blockade induced by human IgG depends mainly on the presence of
"accessible" galactosyl or mannosyl residues in the Fc domain and that the
modulation of the Fc-R function induced by these carbohydrates is due to a change
in the affinity rather than in the number of single class of high-affinity
binding sites.