4 Low affinity antibodies suffice to engage FcγRIIb: abrogating
IgE signalling for single allergens
Using Fel d 1 as a model antigen, we have shown that low affinity IgG
antibodies fail to neutralize the allergen but nevertheless can
efficiently block mast cell/basophil activation21,22.
This unexpected finding was entirely FcγRIIb dependent. Furthermore, the
low affinity antibodies must have a different epitope specificity than
the IgE, as only in this case, low affinity IgG could block mast cell
activation by interaction with FcεRI-bound IgE and engagement of
the inhibitory FcγRIIb. Again, it is likely that lateral diffusion and
avidity stabilization is important in the process, as low affinity IgG
may need to rapidly engage with and be stabilized by FcγRIIb for
effective inhibition of cellular activation. Thus, in this way, also low
affinity IgG antibodies can “poison” IgE-signalling by engaging
FcγRIIb. There is an interesting analogy from enzyme kinetics for the
two types of inhibition. Allergen neutralization corresponds to
competitive inhibition, requiring high affinity ligands for effective
competition. In contrast, engagement of FcγRIIb corresponds to
con-competitive inhibition, rather independent of high affinity23.