3.3 IgG1 and IgG4 prevent primed basophils from degranulation by engaging FcγRIIb
We have previously demonstrated in vitro and in vivo that the allergic reaction mediated by an anti-Fel d 1 IgE of one specificity can be blocked by a single anti-Fel d 1 IgG mAb of a different specificity40,41,37. The mechanism of the inhibition involves the inhibitory FcγRIIβ (Figure 1C). IgE bound on mast cells via the FcεRI can bind to the allergen Fel d 1 formed as complex with IgG. The IgG antibody of the allergen complex may bind to the FcγRIIβ simultaneously, which inhibits the signal cascade of the FcεRI and prevents degranulation. To study the ability of IgG subclasses to drive this process, we performed this experiment to compare IgG1 and IgG4 for their ability to engage the FcγRIIβ. Indeed, both antibody subtypes equally well impeded primed human basophils from degranulation (Figure 3B, D). In addition, while a single IgG-specificity distinct fom the IgE used for priming, was able to block basophil activation, addition of 2 IgGs of different specificities further increased inhibition (Figure 3C, D). Comparison of the inhibition obtained with IgG1 and IgG4 antibody subclasses show no appreciable overall difference between the subclasses. The only minor exception was basophils primed with IgE A044 and then incubated Fel d 1 immune-complexed with IgG1 or IgG4, where inhibition was greater with IgG1 compared to IgG4. This was, however, not the case when basophils were primed with either IgE F127 or IgE G078 (Figure 3 C, D). Thus, IgG1 is at least as potent as IgG4 at blocking basophil activation.