Undergraduate Researcher Univ. of Chicago Chicago, Illinois, United States
Disclosure(s):
Aidan Choi, BS: No financial relationships to disclose
Introduction/Rationale: Understanding how environmental allergens elicit bronchus-associated lymphoid tissue (BALT) is key to elucidating mechanisms of asthma pathophysiology; however, the extent to which different allergens elicit BALT and IgE responses is poorly understood. We previously reported that intratracheal administration of VEGF-C drives lymphangiogenesis and increases BALT and IgE, but their pathogenicity was unclear.
Methods: To investigate this, we exposed mice intratracheally to house dust mite, Alternaria, and ragweed allergens and assessed BALT via fluorescence microscopy. Additionally, we implemented NP-conjugated OVA to measure IgE affinity and to distinguish high affinity (anaphylactic) from low affinity (protective) IgE responses.
Results: All allergens induced BALT, with Alternaria eliciting a stronger response, suggesting differential immune activation and lymphoid tissue formation to environmental allergens. ELISA with NP2, NP7 and NP36 conjugated antigens showed that VEGF-C driven BALT increased the NP2-to-NP36 IgE ratio, indicating a skew towards high affinity anaphylactic IgE responses. Furthermore, following allergen inhalation, VEGF-C treated mice exhibited exacerbated hypothermia, associated with worse anaphylaxis. By contrast, no significant difference was observed between the control and VEGF-C treated groups upon intravenous allergen exposure, implying a lung-localized response. Indeed, VEGF-C treated mice showed increased airway hyperresponsiveness to increasing methacholine, indicative of exacerbated local reactivity. Finally, in B cells within the BALT, we identified Iε transcripts, a necessary event delineating B cells poised to IgE class switching.
Conclusion: Overall, these findings demonstrate that environmental allergens promote BALT and that VEGF-C enhances this process by driving local high affinity IgE production, anaphylaxis and airway hyperresponsiveness. These results suggest that BALT is not only a site for immune activation but also a local source of IgE-producing B cells.
