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

Abstract

Nasal vaccination elicits a humoral immune response that provides protection from airborne pathogens¹, yet the origins and specific immune niches of antigen-specific IgA-secreting cells in the upper airways are unclear². Here we define nasal glandular acinar structures and the turbinates as immunological niches that recruit IgA-secreting plasma cells from the nasal-associated lymphoid tissues (NALTs)³. Using intact organ imaging, we demonstrate that nasal vaccination induces B cell expansion in the subepithelial dome of the NALT, followed by invasion into commensal-bacteria-driven chronic germinal centres in a T cell-dependent manner. Initiation of the germinal centre response in the NALT requires pre-expansion of antigen-specific T cells, which interact with cognate B cells in interfollicular regions. NALT ablation and blockade of PSGL-1, which mediates interactions with endothelial cell selectins, demonstrated that NALT-derived IgA-expressing B cells home to the turbinate region through the circulation, where they are positioned primarily around glandular acinar structures. CCL28 expression was increased in the turbinates in response to vaccination and promoted homing of IgA⁺ B cells to this site. Thus, in response to nasal vaccination, the glandular acini and turbinates provide immunological niches that host NALT-derived IgA-secreting cells. These cellular events could be manipulated in vaccine design or in the treatment of upper airway allergic responses.