CD23 provides a non-inflammatory pathway for IgE-allergen complexes.

Abstract

BACKGROUND

Type I hypersensitivity is mediated by allergen-specific IgE which sensitizes the high-affinity IgE receptor FcεRI on mast cells and basophils which drive allergic inflammation upon secondary allergen contact. CD23/FcεRII, the low affinity receptor for IgE is constitutively expressed on B cells and has been shown to regulate immune responses. Simultaneous binding of IgE to FcεRI and CD23 is blocked by reciprocal allosteric inhibition suggesting that the two receptors exert distinct roles in IgE handling.

OBJECTIVE

We aimed to study how free IgE versus pre-complexed IgE-allergen immune complexes (IgE-ICs) target the two IgE receptors FcεRI and CD23 and we investigated the functional implications of the two pathways.

METHODS

We performed binding and activation assays with human cells in vitro and IgE pharmacokinetics and anaphylaxis experiments in vivo.

RESULTS

We demonstrate that FcεRI preferentially binds free IgE while CD23 preferentially binds IgE-ICs. We further show that those different binding properties directly translate to distinct biological functions: free IgE initiates allergic inflammation via FcεRI on allergic effector cells while IgE-ICs are non-inflamatory due to reduced FcεRI binding and enhanced, CD23-dependent serum clearance.

CONCLUSION

We propose that IgE-ICs are non-inflammatory through reduced engagement by FcεRI but increased targeting of the CD23 pathway.