title: Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge.
abstract: BACKGROUND
  Allergen-specific IgE antibodies are responsible for the pathogenesis of type I hypersensitivity. In patients with allergy, IgE titers can persist in the apparent absence of allergen for years. Seasonal allergen exposure triggers clinical symptoms and enhances allergen-specific IgE. Whether allergen-specific plasma cells originating from seasonal allergen exposures can survive and become long-lived is so far unclear.
  
  
  OBJECTIVE
  We analyzed the localization and lifetimes of allergen-specific IgE-secreting, IgA-secreting, and IgG(1)-secreting plasma cells after allergen inhalation in an ovalbumin-induced murine model of allergic asthma.
  
  
  METHODS
  Ovalbumin-specific IgG(1)-secreting, IgA-secreting, and IgE-secreting cells in lungs, spleen, and bone marrow were isolated and tested for antibody secretion by the ELISpot technique. Longevity of ovalbumin-specific plasma cells was determined by cyclophosphamide treatment, which depletes proliferating plasmablasts but leaves plasma cells untouched. Ovalbumin aerosol-induced infiltrates in lungs were localized by confocal microscopy.
  
  
  RESULTS
  Long-lived ovalbumin-specific plasma cells were generated by systemic sensitization and survived in bone marrow and spleen, maintaining systemic ovalbumin-specific titers of IgG, IgA, and IgE. On inhalation of ovalbumin-containing aerosol, sensitized mice developed airway inflammation and more ovalbumin-specific IgG(1)-secreting, IgA-secreting, and IgE-secreting cells in the lungs and in secondary lymphoid organs. These plasma cells joined the pool of ovalbumin-specific plasma cells in the bone marrow and became long-lived-that is, they are resistant to cyclophosphamide. Termination of ovalbumin inhalation depleted ovalbumin-specific plasma cells from the lungs, but they persisted in spleen and bone marrow.
  
  
  CONCLUSIONS
  Our results show that inhalation of aerosolized allergen generates long-lived, allergen-specific IgG(1)-secreting, IgA-secreting, and IgE-secreting plasma cells that survive cytostatic treatment.
authors.affiliation: DRFZ, German Rheumatism Research Center, Berlin, Germany. luger@drfz.de
authors.forename: Elke O
authors.initials: EO
authors.lastname: Luger
authors.forename: Verena
authors.initials: V
authors.lastname: Fokuhl
authors.forename: Michael
authors.initials: M
authors.lastname: Wegmann
authors.forename: Melanie
authors.initials: M
authors.lastname: Abram
authors.forename: Kati
authors.initials: K
authors.lastname: Tillack
authors.forename: Gernot
authors.initials: G
authors.lastname: Achatz
authors.forename: Rudolf A
authors.initials: RA
authors.lastname: Manz
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Harald
authors.initials: H
authors.lastname: Renz
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000097:blood; D007073:Immunoglobulin E / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010950:Plasma Cells / Q000187:drug effects / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; D003520:Cyclophosphamide; D010047:Ovalbumin