Lung-resident memory B cells maintain allergic IgE responses in the respiratory tract.

Although allergen-specific immunoglobulin E (IgE) is a key mediator of allergic asthma, IgE-expressing B cells fail to form memory B cells (MBCs). Here, we studied the cellular mechanisms supporting IgE production in the respiratory tract. Allergen inhalation induced B cell infiltration into the lungs and IgE in the airway. Tracking B cells poised to class switch to IgE in reporter mice revealed predominant IgE class switching in the lung and identified IgG1(+) MBCs as precursors of IgE-producing cells, which was supported by B cell receptor (BCR) repertoire sequencing. B cells localized with CD4(+) T cells in peribronchiolar lymphoid aggregates. In coculture, interleukin-4 from lung Th2 cells induced lung MBCs to class switch to IgE. Lung-resident MBCs expanded after antigen rechallenge, concurrent with the emergence of IgE-secreting plasma cells (PCs), and the production of IgE in the airway was independent of systemic IgE in circulation, as indicated by parabiosis. Thus, lung-resident IgG1(+) MBCs are cellular precursors for IgE-secreting PCs in the respiratory mucosa.