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Little is known about when, where, and how BAFF is produced in vivo and about which BAFF-producing cells contribute to B cell responses. To better understand BAFF functions, we created BAFF reporter (BAFF-RFP) mice and Baff floxed (Bafffl\/fl) mice. Splenic and bone marrow neutrophils (Nphs) from BAFF-RFP mice expressed the highest constitutive levels of BAFF; other myeloid subsets, including conventional dendritic cells (cDCs) and monocyte (MO) subsets, expressed lower levels. Treatment of BAFF-RFP mice with polyinosinic:polycytidylic acid increased BAFF expression in splenic Ly6Chi inflammatory MOs, CD11bhi activated NK subset, and in bone marrow myeloid precursors. Postinfection with West Nile virus (WNV), BAFF increased in CD8\u2212 cDCs and Nphs, and BAFF+ CD11bhi NK cells expanded in draining lymph nodes. The cell- and tissue-specific increases in BAFF expression were dependent on type I IFN signaling. MAVS also was required or contributed to BAFF expression in dendritic cell and MO subsets, respectively. Mice with deletion of Baff in either cDCs or Nphs had reduced Ab responses after NP-Ficoll immunization; thus, BAFF produced by both cDCs and Nphs contributes to T cell\u2013independent Ab responses. Conversely, mice with a cDC Baff deficiency had increased mortality after WNV infection and decreased WNV-specific IgG and neutralizing Ab responses. BAFF produced by Nphs and cDCs is regulated differently and has key roles in Ab responses and protective immunity.<\/jats:p>","DOI":"10.4049\/jimmunol.1901120","type":"journal-article","created":{"date-parts":[[2020,2,7]],"date-time":"2020-02-07T15:05:13Z","timestamp":1581087913000},"page":"1508-1520","source":"Crossref","is-referenced-by-count":41,"title":["BAFF Produced by Neutrophils and Dendritic Cells Is Regulated Differently and Has Distinct Roles in Antibody Responses and Protective Immunity against West Nile Virus"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-7017","authenticated-orcid":false,"given":"Daniela","family":"Giordano","sequence":"first","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runa","family":"Kuley","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin E","family":"Draves","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4319-3696","authenticated-orcid":false,"given":"Kelsey","family":"Roe","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8122-7965","authenticated-orcid":false,"given":"Ursula","family":"Holder","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7284-514X","authenticated-orcid":false,"given":"Natalia V","family":"Giltiay","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8061-5475","authenticated-orcid":false,"given":"Edward A","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"},{"name":"Division of Rheumatology, Department of Medicine, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,15]]},"reference":[{"key":"2025030417511091800_r1","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nri2572","article-title":"Cracking the BAFF code","volume":"9","author":"Mackay","year":"2009","journal-title":"Nat. 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