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However, the site and mechanisms that regulate this process are poorly defined. Here, we show that while circulating memory B cells entered the lung during rechallenge and were activated within inducible bronchus-associated lymphoid tissues (iBALTs), resident memory B (BRM) cells responded earlier, and their activation occurred in a different niche: directly near infected alveoli. This process required NK cells but was largely independent of CD4 and CD8 T cells. Innate stimuli induced by virus-like particles containing ssRNA triggered BRM cell differentiation in the absence of cognate antigen, suggesting a low threshold of activation. In contrast, expansion of PCs in iBALTs took longer to develop and was critically dependent on CD4 T cells. Our work demonstrates that spatially distinct mechanisms evolved to support pulmonary secondary PC responses, and it reveals a specialized function for BRM cells as guardians of the alveoli.<\/jats:p>","DOI":"10.1084\/jem.20232014","type":"journal-article","created":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T02:21:11Z","timestamp":1712024471000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Regulation of pulmonary plasma cell responses during secondary infection with influenza virus"],"prefix":"10.1084","volume":"221","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-8378-4141","authenticated-orcid":true,"given":"Andrew J.","family":"MacLean","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford, Kennedy Institute of Rheumatology 1 , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5505-8435","authenticated-orcid":true,"given":"Joao P.P.L.","family":"Bonifacio","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford, Kennedy Institute of Rheumatology 1 , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6077-2940","authenticated-orcid":true,"given":"Sophia L.","family":"Oram","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford, Kennedy Institute of Rheumatology 1 , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3510-9148","authenticated-orcid":true,"given":"Mona O.","family":"Mohsen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02k7v4d05","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Bern, Rheumatology, Immunology and Allergology 3 Department of Bio Medical Research, , Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4370-2099","authenticated-orcid":true,"given":"Martin F.","family":"Bachmann","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford, The Jenner Institute 2 Nuffield Department of Medicine, , Oxford, UK"},{"id":[{"id":"https:\/\/ror.org\/02k7v4d05","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Bern, Rheumatology, Immunology and Allergology 3 Department of Bio Medical Research, , Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4629-5820","authenticated-orcid":true,"given":"Tal I.","family":"Arnon","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/052gg0110","id-type":"ROR","asserted-by":"publisher"}],"name":"University of Oxford, Kennedy Institute of Rheumatology 1 , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2024,4,25]]},"reference":[{"key":"2024042513430308300_bib1","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1084\/jem.20142284","article-title":"Distinct germinal center selection at local sites shapes memory B cell response to viral escape","volume":"212","author":"Adachi","year":"2015","journal-title":"J. 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