An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor FcγRIIb.

Zha, Lisha; De Souza Leoratti, Fabiana Maria; He, Lichun; Mohsen, Mona Omar Mahmoud; Cragg, Mark; Storni, Federico Lorenzo; Vogel, Monique; Bachmann, Martin (2018). An unexpected protective role of low-affinity allergen-specific IgG through the inhibitory receptor FcγRIIb. The Journal of allergy and clinical immunology, 142(5), 1529-1536.e6. Elsevier 10.1016/j.jaci.2017.09.054

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BACKGROUND Induction of allergen-specific IgG antibodies is a critical parameter for successful allergen-specific immunotherapy. IgG antibodies can inhibit IgE-mediated mast cell activation through direct allergen neutralization or through the inhibitory receptor FcγRIIb. The affinity of IgE antibodies to the allergen has been shown to be critical for cellular activation. OBJECTIVE Here we addressed the question of affinity thresholds of allergen-specific IgG antibodies for inhibition of mast cell activation using 2 different mAbs against the major cat allergen Fel d 1 both in vitro and in vivo in mice. METHODS Sequences of the 2 high-affinity mAbs were back-mutated to germline, resulting in low-affinity (10 mol/L) antibodies of the exact same specificity. RESULTS Using these newly generated recombinant antibodies, we demonstrate that low-affinity antibodies are still able to inhibit mast cell activation through FcγRIIb but do not neutralize the allergen. CONCLUSION Antibody affinity dictates the mechanism of mast cell inhibition, and IgG antibodies triggering the inhibitory FcγRIIb pathway can show a broader cross-reactivity pattern than previously thought. This indicates that allergen-specific immunotherapy generates a larger protective umbrella of inhibitory IgG antibodies than previously appreciated.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Rheumatology, Clinical Immunology and Allergology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Rheumatologie

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Zha, Lisha; De Souza Leoratti, Fabiana Maria; Mohsen, Mona Omar Mahmoud; Storni, Federico Lorenzo; Vogel, Monique and Bachmann, Martin

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1097-6825

Publisher:

Elsevier

Language:

English

Submitter:

Valery Beer

Date Deposited:

01 Apr 2019 15:35

Last Modified:

01 Apr 2019 15:35

Publisher DOI:

10.1016/j.jaci.2017.09.054

PubMed ID:

29391255

Uncontrolled Keywords:

Allergy FcγRIIb-mediated inhibition Fel d 1 low-affinity antibodies vaccination

BORIS DOI:

10.7892/boris.125727

URI:

https://boris.unibe.ch/id/eprint/125727

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