Induction of long-lived allergen-specific plasma cells by mucosal allergen challenge

J Allergy Clin Immunol. 2009 Oct;124(4):819-26.e4. doi: 10.1016/j.jaci.2009.06.047.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Animals
  • Asthma / immunology*
  • Asthma / metabolism
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • Cyclophosphamide / pharmacology
  • Disease Models, Animal
  • Female
  • Immunity, Mucosal
  • Immunoglobulin A / blood
  • Immunoglobulin E / blood*
  • Immunoglobulin G / blood
  • Immunosuppressive Agents / pharmacology
  • Lung / immunology
  • Lung / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / immunology
  • Plasma Cells / drug effects
  • Plasma Cells / immunology*
  • Spleen / immunology
  • Spleen / metabolism

Substances

  • Allergens
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Immunoglobulin E
  • Cyclophosphamide
  • Ovalbumin