An unexpected protective role of low affinity allergen-specific IgG via the inhibitory receptor FcγRIIb

Publication date: Available online 31 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Martin Bachmann, Monique Vogel, Lisha Zha, Fabiana Leoratti, Lichun He, Mona O. Mohsen, Federico Storni, Mark Cragg
BackgroundInduction of allergen-specific IgG antibodies is a critical parameter for successful specific immunotherapy (SIT). IgG antibodies may inhibit IgE-mediated mast cell activation by direct allergen-neutralization or via the inhibitory receptor FcγRIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation.ObjectiveHere we addressed the question of the affinity thresholds of allergen-specific IgG antibodies for inhibition of mast cell activation by using 2 different monoclonal antibodies against the major cat allergen, Fel d 1, both in vitro and in vivo in mice.MethodsThe sequences of the two high-affinity mAbs were back-mutated to germ-line, resulting in low affinity (10^-7M) antibodies of the exact same specificity.ResultsUsing these newly generated recombinant antibodies, we demonstrate that low affinity antibodies are still able to inhibit mast cell activation via FcγRIIb but fail to neutralize the allergen.ConclusionAntibody affinity dictates the mechanism of mast cell inhibition and IgG antibodies triggering the inhibitory FcγRIIb-pathway may show a broader cross-reactivity pattern than previously thought. This indicates that SIT generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated.

Graphical abstract

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