Inhibition of rBet v 1-induced basophil histamine release with specific immunotherapy-induced serum immunoglobulin G:: no evidence that FcγRIIB signalling is important

Background Human basophils and mast cells express the low-affinity immunoglobulin (Ig)G receptor Fc gamma RIIB. It has previously been shown in artificial model systems that cross-linking of the high-affinity IgE receptor Fc epsilon RI and Fc gamma RIIB leads to inhibition of Fc epsilon RI signalling. Objective The aim of the present study was to investigate whether cross-linking of Fc epsilon RI and Fc gamma RIIB contributes to IgG-mediated inhibition of histamine release in human basophils in a system using the sera from specific immunotherapy (SIT) patients and the major allergen from birch pollen, Bet v 1. As IgG4 furthermore has been proposed to have special blocking properties, we investigated the significance of IgG subclass specificity for this inhibition. Methods Binding of recombinant Bet v 1-IgG complexes to Fc gamma RII and IgG-binding activities in the sera from 25 birch pollen-allergic patients treated with SIT were measured using I-125-rBet v 1. Inhibition of basophil histamine release was assessed by incubating washed leucocytes with complexes of rBet v 1-IgG with or without blocking of Fc gamma RII. Results We observed low binding of rBet v 1-IgG complexes to Fc gamma RII, which was negatively correlated with the relative IgG4-binding activities. Blocking of Fc gamma RII did not reverse the SIT-IgG-induced inhibition of basophil histamine release. However, IgG-binding activities correlated significantly with the ability of the SIT sera to inhibit basophil histamine release. Conclusion We suggest that at least in birch pollen SIT, the contribution of Fc gamma RIIB-mediated inhibitory signalling to SIT-IgG-induced inhibition of human basophil histamine release is of minor importance. The main contributor to the inhibitory effect of SIT-induced IgG seems to be blocking of the allergen-IgE interaction.