C34-15 B Cells Orchestrate Lung Inflammation and Remodeling in a House Dust Mite Driven Airway Inflammation Mouse Model

Background B cells are traditionally recognized for their role in the production of allergen-specific antibodies during airway inflammation. Emerging studies suggest that B cells may also participate directly in local immune responses within the lung. However, the precise localization and contribution of lung B cells to the pathological processes such as tissue remodeling remains unclear. This study explores the accumulation and functional role of B cells in the lung with emphasis on their potential involvement in ectopic follicle formation, antibody production, and tissue remodeling. Methods Mice were intranasally exposed to house dust mite (HDM) extract three times weekly for up to 15 weeks, while control animals received saline. Lung B cell populations were analyzed via flow cytometry. To determine the impact of B cells on allergic airway inflammation, HDM-exposed mice underwent B cell depletion with anti-CD19 and anti-CD20 antibodies for 10 weeks, beginning at week 15. Bulk RNA sequencing of lung tissues from both B cell-depleted and control mice was performed to identify transcriptomic changes associated with B cell absence during chronic inflammation. Results Chronic HDM exposure led to the accumulation of B cells around the airways, where they formed organized lymphoid aggregates. These B cells differentiated into plasma cells and produced anti-elastin antibodies detectable both locally and systemically. B cell depletion following allergen exposure resulted in a pronounced reduction in lung inflammation and tissue remodeling, accompanied by decreased anti-elastin antibody levels. Transcriptomic analysis revealed that B cells play a critical role in driving local inflammation and tissue remodeling. Specifically, pathways associated with antibody production, B cell activation, and extracellular matrix organization were differentially modulated in B cell-depleted mice compared to controls. Conclusions Our findings highlight the critical role of B cells in contributing to lung inflammation and remodeling during allergic airway inflammation by producing anti-elastin antibodies and organizing local immune structures. Targeted B cell depletion mitigated this pathological process, suggesting that B cells and their antibody products play a key role in lung remodeling. This abstract is funded by: Regeneron