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.