Type I hypersensitivity, also known as classical allergy, is mediated
via allergen-specific IgE antibodies bound to type I FcR (FcεRI) on the
surface of mast cells and basophils upon cross-linking by allergens.
This IgE-mediated cellular activation may be blocked by
allergen-specific IgG through multiple mechanisms, including direct
neutralization of the allergen or engagement of the inhibitory receptor
FcγRIIb which blocks IgE signal transduction. In addition, co-engagement
of FceRI and FcγRIIb by IgE-IgG-allergen immune-complexes causes
down-regulation of receptor bound IgE, resulting in desensitization of
the cells. Both, activation of FceRI by allergen-specific IgE and
engagement of FcγRIIb by allergen-specific IgG are driven by
allergen-binding. Here we delineate the distinct roles of antibody
affinity versus avidity in driving these processes and discuss the role
of IgG subclasses in inhibiting basophil and mast cell activation.