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Nasal vaccination aims to induce local protection in the upper airway mucosa. Although B cell\u2013driven immunity is well characterized in gut-associated lymphoid tissues such as Peyer\u2019s patches and mesenteric LNs, much less is known about analogous processes in the upper airways. Here, we show that B cell receptor (BCR) affinity and CCR6 regulate germinal center (GC) seeding and class-switch recombination (CSR) to IgA in nasal-associated lymphoid tissue (NALT) following nasal vaccination. B cells bearing low-affinity BCRs failed to upregulate CCR6 and did not support T follicular helper cell differentiation or seed GCs in the NALT. CCR6-deficient B cells were unable to migrate to the NALT subepithelial dome or undergo IgA CSR and seed GC effectively in response to nasal vaccination or commensal bacteria signals. Thus, effective targeting of B cell clones to induce CCR6 expression is essential for nasal vaccine design.<\/jats:p>","DOI":"10.1084\/jem.20251901","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T07:20:53Z","timestamp":1768980053000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Nasal germinal centers and IgA class-switch recombination depend on CCR6 and B cell receptor affinity"],"prefix":"10.1084","volume":"223","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5907-9919","authenticated-orcid":true,"given":"Jingjing","family":"Liu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Weizmann Institute of Science 1 Department of Systems Immunology, , Rehovot,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8194-9979","authenticated-orcid":true,"given":"Liat","family":"Stoler-Barak","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Weizmann Institute of Science 1 Department of Systems Immunology, , Rehovot,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9604-212X","authenticated-orcid":true,"given":"Ziv","family":"Shulman","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0316ej306","id-type":"ROR","asserted-by":"publisher"}],"name":"Weizmann Institute of Science 1 Department of Systems Immunology, , Rehovot,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2026,2,10]]},"reference":[{"key":"2026021009525520900_bib1","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.immuni.2017.04.004","article-title":"Regionalized development and maintenance of the intestinal adaptive immune landscape","volume":"46","author":"Agace","year":"2017","journal-title":"Immunity"},{"key":"2026021009525520900_bib2","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1016\/j.immuni.2012.11.020","article-title":"Persistent antigen and germinal center B cells sustain T follicular helper cell responses and phenotype","volume":"38","author":"Baumjohann","year":"2013","journal-title":"Immunity"},{"key":"2026021009525520900_bib3","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.it.2024.01.006","article-title":"Gut-associated lymphoid tissue: A microbiota-driven hub of B cell immunity","volume":"45","author":"Bemark","year":"2024","journal-title":"Trends Immunol."},{"key":"2026021009525520900_bib4","doi-asserted-by":"publisher","first-page":"7772","DOI":"10.4049\/jimmunol.177.11.7772","article-title":"Gut IgA class switch recombination in the absence of CD40 does not occur in the lamina propria and is independent of germinal centers","volume":"177","author":"Bergqvist","year":"2006","journal-title":"J. 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