A novel IgA plasma cell niche in the human airways

IgA antibodies secreted into the airways by B plasma cells are vital for pathogen neutralisation and mucosal immunity in the lungs. However, the cell-cell interactions that recruit B plasma cells and locally support their function is largely unknown. We sequenced deep tissue samples from healthy human airways with single cell and spatial technologies to resolve an IgA plasma niche, including naïve B cells and CD4 T cells, at the submucosal glands (SMG). We define the human transcriptome of SMG duct cells, which can recruit IgA plasma cells through the CCL28-CCR10 axis and support their survival, maturation and antibody production through expression of APRIL and IL6. In addition, we show that SMG epithelial cells express MHC-II and CD40 and co-localise with CD4 T cells, suggesting a role for antigen presentation and local induction of T cell dependent B cell responses. Overall our work defines a previously unknown niche for IgA plasma cells in the airway SMG, demonstrating the power of integrating single cell and spatial transcriptomic datasets. Along with filling a major gap in mucosal immunity, this niche may be implicated in lung diseases and respiratory infections. Using this knowledge to manipulate or enhance IgA responses, for example in a vaccine setting, could become an important avenue for improving lung health.