Lymphoid aggregates accumulate in the lung during allergen-driven airway inflammation and serve as a local source of IgE production

Lymphoid aggregates (LAs) can develop in the lung in response to infection or chronic inflammation. Allergen-induced inflammation may drive LA formation in inflamed lung, and once established, the presence of pulmonary LAs may serve as a dynamic site of IgE production directly in the mucosal site. Here, we investigate the composition of LA and their role in local IgE+ PCs development after house dust mite (HDM) allergen exposure. We show that short-term allergen exposure (4 weeks) resulted in the generation of LAs composed of B cells, CD4+ T cells and follicular DCs in the lung. IgE+ PCs also accumulated in the lung after short-term allergen exposure and found that over 90% of IgE+ PCs are tissue-resident. Notably, LA are found in close proximity to airway epithelial cells, while IgE+ PCs are localized outside of major lymphoid aggregates. Finally, we demonstrate that chronic exposure to HDM could generate long-lived IgE PCs present in the lung, even when de novo production of IgE was interrupted with either persistent B cell depletion or anti-IL-4Ra to block IgE class switching. These data demonstrate that IgE+ PCs arise during acute HDM exposure in non-lymphoid lung tissues where allergic inflammation is occurring, localize near the airway, and keep accumulating during chronic allergic inflammation. The inflamed lung can thus provide a survival niche for long-lived IgE+ PCs that can contribute to local IgE production.