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.
Original language | English |
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Pages (from-to) | 637-646 |
Number of pages | 10 |
Journal | Nature |
Volume | 632 |
Issue number | 8025 |
DOIs | |
Publication status | Published Online - 31 Jul 2024 |
Funding
Z.S. is supported by the European Research Council (ERC) grant no. 101001613, Israel Science Foundation (ISF) grant no. 1272/23 and the Morris Kahn Institute for Human Immunology. Z.S. is a member of the European Molecular Biology Organization (EMBO) Young Investigator Program. We thank M. Bemark (University of Lund) for discussions and comments about the study and D. Farfara for help in mouse head sectioning (Technion-Israel Institute of Technology). Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature Limited 2024.
All Science Journal Classification (ASJC) codes
- General