Local synthesis of epsilon germline gene transcripts, IL-4, and IL-13 in allergic nasal mucosa after ex vivo allergen exposure

J Allergy Clin Immunol. 2000 Jul;106(1 Pt 1):46-52. doi: 10.1067/mai.2000.107398.

Abstract

Background: The production of epsilon germline gene transcripts (Iepsilon(+)/Cepsilon(+) RNA) precedes class switch recombination to IgE and is induced by IL-4 and/or IL-13. Although Iepsilon and Cepsilon RNA(+) B cells have been identified within nasal tissue after in vivo allergen exposure, suggesting local germline transcription, whether these were resident or infiltrating B lymphocytes was not clear.

Objective: We sought to examine whether B cells resident to the nasal mucosa undergo epsilon germline transcription.

Methods: Nasal mucosal biopsy specimens were obtained from asymptomatic patients with seasonal allergic rhinitis and exposed to allergen ex vivo. Using immunocytochemistry, B lymphocytes were enumerated; with in situ hybridization, the number of cells expressing Iepsilon, Cepsilon, IL-4, and IL-13 messenger (m)RNA(+) cells was examined.

Results: Tissue cultured in medium containing specific allergen exhibited significantly more Iepsilon and Cepsilon RNA(+) cells compared with medium alone (P <.05). IL-4 and IL-13 mRNA synthesis also resulted from ex vivo allergen exposure; there were significantly more cells expressing transcripts for these cytokines within allergic nasal mucosal tissue cultured with allergen than medium alone (P <.05). Within allergen-stimulated tissue obtained from allergic patients, 30% of total B cells were Iepsilon RNA(+), and the majority of IL-4 and IL-13 mRNA(+) cells were T cells (68% and 44%, respectively) and mast cells (32% and 19%, respectively).

Conclusion: These results demonstrate that the nasal mucosa is a site of epsilon germline gene transcription and suggest that local T cell and mast cell production of IL-4 and IL-13 may regulate this event.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / pharmacology
  • Antigens, CD20 / analysis
  • B-Lymphocytes / immunology
  • Culture Techniques
  • Humans
  • Immunoglobulin Constant Regions / genetics*
  • Immunoglobulin Switch Region / genetics*
  • Immunoglobulin epsilon-Chains / genetics*
  • Immunohistochemistry
  • Interleukin-13 / biosynthesis
  • Interleukin-13 / genetics
  • Interleukin-13 / physiology*
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Interleukin-4 / physiology*
  • Mast Cells / metabolism
  • Nasal Mucosa / immunology*
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / metabolism
  • T-Lymphocytes / metabolism
  • Transcription, Genetic*

Substances

  • Allergens
  • Antigens, CD20
  • Immunoglobulin Constant Regions
  • Immunoglobulin epsilon-Chains
  • Interleukin-13
  • RNA, Messenger
  • Interleukin-4