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

Abstract

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