title: High-dose bee venom exposure induces similar tolerogenic B-cell responses in allergic patients and healthy beekeepers.
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+BR1 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.
authors.affiliation: 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.
authors.forename: T
authors.initials: T
authors.lastname: Boonpiyathad
authors.affiliation: Department of Rheumatology, Clinical Immunology and Allergology, University Hospital, Bern, Switzerland.
authors.forename: N
authors.initials: N
authors.lastname: Meyer
authors.affiliation: 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.
authors.forename: M
authors.initials: M
authors.lastname: Moniuszko
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Sokolowska
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.|Department of Regenerative Medicine and Immune Regulation, Medical University of Bialystok, Bialystok, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Eljaszewicz
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.
authors.forename: O F
authors.initials: OF
authors.lastname: Wirz
authors.affiliation: Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: M M
authors.initials: MM
authors.lastname: Tomasiak-Lozowska
authors.affiliation: Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
authors.forename: A
authors.initials: A
authors.lastname: Bodzenta-Lukaszyk
authors.affiliation: Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
authors.forename: K
authors.initials: K
authors.lastname: Ruxrungtham
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zürich, Davos, Switzerland.|Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland.
authors.forename: W
authors.initials: W
authors.lastname: van de Veen
mesh_terms: D000485:Allergens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001514:Bee Venoms / Q000276:immunology*; D015415:Biomarkers; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic / Q000379:methods; D004306:Dose-Response Relationship, Immunologic; D004781:Environmental Exposure / Q000009:adverse effects*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D007108:Immune Tolerance; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D016273:Occupational Exposure; D054467:Phospholipases A2 / Q000378:metabolism
chemical_list: D000485:Allergens; D001514:Bee Venoms; D015415:Biomarkers; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D054467:Phospholipases A2
keywords: CCR5; IgG4; Regulatory B cells; allergen-specific immunotherapy; bee venom allergy; immune tolerance