Shaping of B cell responses and the repertoire of allergen-specific antibodies by allergen immunotherapy (FWF title: B cell and antibody repertoires in allergen immunotherapy)

• Applicants: Dr. Christian Möbs; Professor Dr. Wolfgang Pfützner
• Subject Area: Clinical Immunology and Allergology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 564137475

Allergen immunotherapy (AIT) is the only causative treatment for IgE-mediated allergies. Although performed for more than 100 years, the immune mechanisms resulting in allergen tolerance are still not entirely clear. Successful AIT has been associated with the induction of IL-10 secreting B cells and recently, the significance of allergenblocking antibodies (Abs) for the reduction of allergic symptoms has been demonstrated. Still, the precise role of different types of B cells in the development of tolerance and its maintenance after cessation of AIT has not been closely investigated. Also, details about the AIT-induced repertoire of allergen-specific Abs are still missing, e.g. whether the clonal complexity of therapy-induced Abs is restricted to only a few or many clones, and whether the repertoires of AIT-induced IgG Abs are durable, or wax and wane in the course of therapy. These knowledge gaps tempted the three partners Bohle/Möbs/Pfützner to conjointly investigate how AIT shapes allergen-specific B cell responses and antibody repertoires. This project will employ birch pollen allergy and the major allergen Bet v 1 to longitudinally characterize and monitor AIT-induced i) allergen-specific B cell subsets and their interaction with AIT-modified T helper cell subtypes regarding Ab production (major goal of Möbs/Pfützner), and ii) clonal repertoires of circulating allergen-specific IgE, IgG1, and IgG4 Abs and their role as blocking Abs (major goal of Bohle). All partners will study peripheral blood mononuclear cells and serum samples from the same individuals regularly collected before, during, and after cessation of conventional AIT with birch pollen including two off-treatment birch pollen seasons. B cell subsets will be analyzed by flow cytometry and the BD Rhapsody system which allows single-cell analysis by combining transcriptomics and proteomics. Sorted T helper cell subsets will be co-cultured with B cells and the resulting Ab isotypes will be characterized including their affinity and IgE-blocking activity. The clonal complexity of circulating AIT-induced allergen-specific IgG1 and IgG4 Abs will be studied ex vivo by reversed-phase liquid chromatography mass spectrometry of their Fab fragments and by epitope mapping with Bet v 1-chimeric proteins. In summary, this project will reveal a plethora of information on the individual allergen-specific B cell-responses induced by and maintained after AIT. The shaping of B cell and Ab repertoires will be correlated with the clinical efficacy of treatment. Thus, the here proposed continued cooperation of three partners with high expertise and experience in allergen-specific cellular and humoral responses will enhance the knowledge about relevant immune processes of AIT-induced tolerance to allergens. The insights gained from the project will contribute to both prevention and more efficient treatment of IgE-mediated allergy.

• DFG Programme: Research Grants
• International Connection: Austria
• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partner: Professorin Dr. Barbara Bohle