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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.

Author information

1
Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
2
Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailand.
3
Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
4
Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
5
Department of Rheumatology, Clinical Immunology and Allergology, University Hospital, Bern, Switzerland.
6
Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
7
Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

KEYWORDS:

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

PMID:
27341567
DOI:
10.1111/all.12966
[Indexed for MEDLINE]

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