Turbinate-homing IgA-secreting cells originate in the nasal lymphoid tissues

Nasal vaccination elicits a humoral immune response that protects from airborne pathogens, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways remain unknown. Here, we define glandular acinus of nasal turbinate as an immunological niche recruits IgA-secreting cells from the nasal-associated lymphoid tissues (NALT) in response to intranasal vaccination. Using intact organ imaging, we investigated the cellular events that support antibody-mediated immune responses in mouse upper airways. Through visualization of antigen-specific T and B cells within intact organs in the upper airways, we demonstrate that nasal vaccination induced extensive B cell expansion in the subepithelial dome (SED) of NALT, followed by invasion into commensal bacteria-driven chronic germinal centers (GCs) in a T cell-dependent manner. Antigen-specific B cell response in the NALT required pre-expansion of cognate T cells, which initiate the immune response in the inter-follicular regions of NALT, and occurred effectively in the presence of Monophosphoryl-Lipid A (MPLA), a synthetic, non-toxic TLR-4 agonist. NALT ablation and blockade of PSGL-1 demonstrated that intranasal vaccination generates IgA+ plasma cells homing to the nasal turbinate through the blood circulation where they are positioned primarily around glandular acinus structures. Bulk-mRNA sequencing and antibody neutralization assays revealed CCL28 as a major homing signal in the turbinate that attracts NALT plasma cells. Thus, the glandular part of the nasal turbinate is an immunological niche that hosts NALT-derived IgA-secreting cells. These cellular events can be manipulated to design vaccines against inhaled pathogens or in the treatment of upper airway allergic responses.