title: Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells.
abstract: BACKGROUND
  B cells play a central role in IgE-mediated allergies. In damaged airway epithelium, they are exposed directly to aeroallergens. We aimed to assess whether direct exposure of B cells to pollen constituents affects allergic sensitization.
  
  
  METHODS
  B cells from murine splenocytes and from blood samples of healthy donors were incubated for 8 days under Th2-like conditions with aqueous ragweed pollen extracts (Amb-APE) or its constituents. Secreted total IgM, IgG, and IgE was quantified by ELISA. Additionally, birch, grass, or pine-pollen extracts were tested. The number of viable cells was evaluated by ATP measurements. B-cell proliferation was measured by CFSE staining. IgE class switch was analyzed by quantitation of class switch transcripts. In an OVA/Alum i.p.-sensitization mouse model, Amb-APE was intranasally instilled for 11 consecutive days.
  
  
  RESULTS
  Upon Th2 priming of murine B cells, ragweed pollen extract caused a dose-dependent increase in IgE production, while IgG and IgM were not affected. The low-molecular-weight fraction and phytoprostane E1 (PPE1) increased IgE production, while Amb a 1 did not. PPE1 enhanced IgE also in human memory B cells. Under Th1 conditions, Amb-APE did not influence immunoglobulin secretion. The IgE elevation was not ragweed specific. It correlated with proliferation of viable B cells, but not with IgE class switch. In vivo, Amb-APE increased total IgE and showed adjuvant activity in allergic airway inflammation.
  
  
  CONCLUSIONS
  Aqueous pollen extracts, the protein-free fraction of Amb-APE, and the pollen-contained substance PPE1 specifically enhance IgE production in Th2-primed B cells. Thus, pollen-derived nonallergenic substances might be responsible for B-cell-dependent aggravation of IgE-mediated allergies.
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Oeder
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.
authors.forename: F
authors.initials: F
authors.lastname: Alessandrini
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
authors.forename: O F
authors.initials: OF
authors.lastname: Wirz
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center, Georg August University, Göttingen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Braun
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.|Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Wimmer
authors.affiliation: Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.|Institute of Biochemical Plant Pathology, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Frank
authors.affiliation: Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.|Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Hauser
authors.affiliation: Institute of Biochemical Plant Pathology, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Durner
authors.affiliation: Department of Molecular Biology, University of Salzburg, Salzburg, Austria.
authors.forename: F
authors.initials: F
authors.lastname: Ferreira
authors.affiliation: Institute of Biochemical Plant Pathology, Helmholtz Center Munich, Neuherberg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Ernst
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Department of Dermatology, Venereology and Allergology, University Medical Center, Georg August University, Göttingen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Mempel
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.|Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Munich, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Gilles
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.
authors.forename: J T M
authors.initials: JT
authors.lastname: Buters
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.
authors.forename: H
authors.initials: H
authors.lastname: Behrendt
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Christine Kühne - Center for Allergy Research and Education, CK-CARE, Davos, Switzerland.|Institute of Environmental Medicine, UNIKA-T, Technische Universität München, Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Traidl-Hoffmann
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Schmidt-Weber
authors.affiliation: Swiss Institute of Allergy and Asthma Research (SIAF), Davos, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Akdis
authors.affiliation: Center of Allergy and Environment (ZAUM), Technische Universität München and Helmholtz Zentrum München, Member of the German Center for Lung Research (DZL), Munich, Germany.|Department of Dermatology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Gutermuth
mesh_terms: D000485:Allergens / Q000276:immunology*; D031164:Ambrosia / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D052179:Antigens, Plant / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology*; D007156:Immunologic Memory; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D010936:Plant Extracts / Q000276:immunology; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011058:Pollen / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000485:Allergens; D052179:Antigens, Plant; D010936:Plant Extracts; D007073:Immunoglobulin E; D010047:Ovalbumin
keywords: B cell; IgE; adjuvant; phytoprostane E1; pollen