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Allergy. 2017 Mar;72(3):407-415. doi: 10.1111/all.12966. Epub 2016 Jul 20.

High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers.

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Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
Department of Rheumatology, Clinical Immunology and Allergology, University Hospital, Bern, Switzerland.
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.



The involvement of B cells in allergen tolerance induction remains largely unexplored. This study investigates the role of B cells in this process, by comparing B-cell responses in allergic patients before and during allergen immunotherapy (AIT) and naturally exposed healthy beekeepers before and during the beekeeping season.


Circulating B cells were characterized by flow cytometry. Phospholipase A2 (PLA)-specific B cells were identified using dual-color staining with fluorescently labeled PLA. Expression of regulatory B-cell-associated surface markers, interleukin-10, chemokine receptors, and immunoglobulin heavy-chain isotypes, was measured. Specific and total IgG1, IgG4, IgA, and IgE from plasma as well as culture supernatants of PLA-specific cells were measured by ELISA.


Strikingly, similar responses were observed in allergic patients and beekeepers after venom exposure. Both groups showed increased frequencies of plasmablasts, PLA-specific memory B cells, and IL-10-secreting CD73- CD25+ CD71+ BR 1 cells. Phospholipase A2-specific IgG4-switched memory B cells expanded after bee venom exposure. Interestingly, PLA-specific B cells showed increased CCR5 expression after high-dose allergen exposure while CXCR4, CXCR5, CCR6, and CCR7 expression remained unaffected.


This study provides the first detailed characterization of allergen-specific B cells before and after bee venom tolerance induction. The observed B-cell responses in both venom immunotherapy-treated patients and naturally exposed beekeepers suggest a similar functional immunoregulatory role for B cells in allergen tolerance in both groups. These findings can be investigated in other AIT models to determine their potential as biomarkers of early and successful AIT responses.


CCR5; IgG4; Regulatory B cells; allergen-specific immunotherapy; bee venom allergy; immune tolerance

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