Allergen/Igg Immune Complex Co-Aggregation Of Fcgriia And Fcgriib Induces Decreased Intrinsic Basophil Sensitivity Associated With Immunotherapy

The basis of allergen-specific IgG antibody modulation of IgE-mediated basophil activation remains controversial. With IRB approval, three groups were recruited: subjects who were 1) not allergic to cat, 2) allergic to cat but immunotherapy naive, 3) allergic and receiving immunotherapy. Serum allergen-specific IgE and IgG subclasses were quantified. Allergen induced basophil activation was assayed by flow cytometry using whole blood. Blocking antibodies against FcgRIIA or FcgRIIB were added prior to stimulation. Cat-allergen specific IgG was manipulated immunochemically. Responsiveness of basophils from allergic individuals to cat allergen was decreased by the presence of cat allergen specific, IgG-containing sera from immunotherapy subjects. This effect was both IgG dependent and sufficient, and, based on antibody-mediated blocking, required both FcgRIIA and FcgRIIB. Importantly however, basophils from subjects with high cat-specific IgG and chronic exposure to cat allergen were not subject to this acute regulation. IgG anti-allergen antibodies can reduce basophil responsiveness to allergen via engagement of low affinity IgG receptors. Interaction with both FcgIIA and FcgRIIB is required, suggesting that recruitment of FcgRIIA in the absence of FceR1 may initiate transacting inhibitory signaling circuitry via FcgRIIB ITIMs. However, chronic stimulation of these receptors may, by activation of inhibitory signaling, confer a cell intrinsic hypo-responsiveness, such that acute stimulation of FcgRIIB has no further inhibitory effect. The mechanism and duration of this change is under study.