Pollen-derived nonallergenic substances enhance Th2-induced IgE production in B cells

Allergy. 2015 Nov;70(11):1450-60. doi: 10.1111/all.12707. Epub 2015 Aug 28.

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.

Keywords: B cell; IgE; adjuvant; phytoprostane E1; pollen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / immunology*
  • Ambrosia / immunology
  • Animals
  • Antibody Formation / immunology*
  • Antigens, Plant / immunology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Female
  • Humans
  • Immunization
  • Immunoglobulin E / immunology*
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Mice
  • Ovalbumin / immunology
  • Plant Extracts / immunology
  • Pneumonia / immunology
  • Pneumonia / metabolism
  • Pneumonia / pathology
  • Pollen / immunology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism

Substances

  • Allergens
  • Antigens, Plant
  • Plant Extracts
  • Immunoglobulin E
  • Ovalbumin