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 activation 21,22. 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.