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

Jingjing Liu, Liat Stoler-Barak, Hadas Hezroni-Bravyi, Adi Biram, Sacha Lebon, Natalia Davidzohn, Merav Kedmi, Muriel Chemla, David Pilzer, Marina Cohen, Ori Brenner, Moshe Biton and Ziv Shulman ()
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Jingjing Liu: Weizmann Institute of Science
Liat Stoler-Barak: Weizmann Institute of Science
Hadas Hezroni-Bravyi: Weizmann Institute of Science
Adi Biram: Weizmann Institute of Science
Sacha Lebon: Weizmann Institute of Science
Natalia Davidzohn: Weizmann Institute of Science
Merav Kedmi: Weizmann Institute of Science
Muriel Chemla: Weizmann Institute of Science
David Pilzer: Weizmann Institute of Science
Marina Cohen: Weizmann Institute of Science
Ori Brenner: Weizmann Institute of Science
Moshe Biton: Weizmann Institute of Science
Ziv Shulman: Weizmann Institute of Science

Nature, 2024, vol. 632, issue 8025, 637-646

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41586-024-07729-x

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