Transfer of immediate hypersensitivity and airway hyperresponsiveness by IgE-positive B cells.

Abstract

The role of allergen-specific sIgE+ B cells in the development of airway hyperresponsiveness to electrical field stimulation was examined in a murine model of allergic sensitization. Ovalbumin (OVA)-specific B cells (OVA+) were isolated from mice that were sensitized to aerosolized OVA. The OVA+ B cell population was shown to be distinct from the remaining, non-OVA-responsive B cells (OVA-). There was a high frequency of sIgE+ B cells and a low frequency of sIgG+ B cells in the OVA+ population compared with the OVA- population, where the ratio was reversed. Although both populations produced immunoglobulin in vitro, only the OVA+ cells secreted anti-OVA antibodies. Transfer of 10(6) OVA+ B cells or as few as 5 x 10(4) OVA+/sIgE+ B cells was able to transfer the capability for anti-OVA IgE synthesis and cutaneous reactivity to OVA in naive recipients. Exposure to OVA via the airways in addition to transfer of OVA+ B cells was necessary for development of airway hyperresponsiveness, whereas recipients challenged with an irrelevant allergen, ragweed, had normal airway function. Transfer of up to 10(7) OVA- B cells failed to induce production of anti-OVA IgE. Despite production of polyclonal IgE, recipients of OVA- B cells did not develop airway hyperresponsiveness after OVA challenge. We conclude that both allergen-specific IgE production and local challenge via the airways with specific allergen are necessary to change airway function in this model.

Allergen-induced bronchial hyperreactivity and eosinophilic inflammation occur in the absence of IgE in a mouse model of asthma

“…They have shown that BHR, measured by an ex vivo assay, and eosinophilic inflammation after OVA challenge can be passively transferred to naive recipients by IgE or IgE ϩ B cells from animals sensitized to OVA only by inhalation (18). IgE-independent mechanisms involving the generation of allergen-specific CD8 ϩ cells also may participate in pathogenesis in this model (38).…”

“…Nebulized ovalbumin (OVA) has been used to elicit specific IgE responses and bronchial hypersensitivity in mice (17). The passive transfer of IgE ϩ B cells has been shown to confer OVA-inducible BHR in this model (18). Mice bred for high levels of IgE production have been reported to manifest both greater BHR and more eosinophil infiltration in the respiratory epithelium after OVA sensitization and challenge than control animals (19).…”

B Cell Antigen Presentation Promotes Th2 Responses and Immunopathology during Chronic Allergic Lung Disease

“…Previous studies concerning B cells in allergic disease have concluded that B cells play no role in the development of allergic disease as characterized by inflammation, eosinophilia, and AHR [17], [18]. Other studies have suggested that the contribution of B cells is primarily via IgE [19], [20]. Still other studies which support a role for B cells in allergic lung disease did not directly address the mechanism by which B cells contribute to allergic disease [21], [22].…”

Mechanisms of Experimental Mouse Models of Airway Hyperresponsiveness

“…For example, mice lacking B cells or IgE (Mehlop et al, 1997) develop AHR and eosinophilia indistinguishable from control animals. However, transfer of IgE from OVA-sensitized into naïve animals can induce the development of eosinophilia and AHR on exposure to OVA, demonstrating that allergen-specific IgE is sufficient to induce an asthma-like phenotype (Lack et al, 1995), but may not be required.…”