Abstract:
Background : IgE antibodies are involved in type-1
hypersensitivity. Cross-linking IgE bound to the high-affinity IgE
receptor, FceRI on effector cells with an allergen can cause
anaphylaxis. Recent studies have shown that IgE glycosylation
significantly impacts the ability of IgE to bind to its high-affinity
receptor FceRI and exert effector functions. We have recently shown that
immunization of mice with IgE in complex with an allergen leads to a
protective, glycan-dependent anti-IgE response. However, to what extent
the glycans on IgE determine the induction of those antibodies and how
they facilitate serum clearance is unclear.
We investigated the role of glycan-specific IgG anti-IgE autoantibodies
in regulating serum IgE levels and preventing systemic anaphylaxis by
passive immunization.
Methods: Mice were immunized using glycosylated or
deglycosylated IgE-allergen-immune complexes (ICs) to induce anti-IgE
IgG antibodies. The anti-IgE IgG antibodies were purified and used for
passive immunization.
Results : Glycosylated IgE-ICs induced a significantly higher
anti-IgE IgG response and more IgG secreting plasma cells than
deglycosylated IgE-ICs. Passive immunization of IgE sensitized mice with
purified anti-IgE IgG increased the clearance of IgE and prevented
systemic anaphylaxis upon allergen challenge. Anti-IgE IgG purified from
the serum of mice immunized with deglycosylated IgE-ICs, led to a
significantly reduced elimination and protection, confirming that the
IgE glycans themselves are the primary drivers of the protectivity
induced by the IgE-immune complexes.
Conclusion : IgE glycosylation is essential for a robust
anti-IgE IgG response and might be an important regulator of serum IgE
level.