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In this study we used NOS2\u2212\/\u2212 mice to determine the role of NO in T cell\u2013dependent and T cell\u2013independent (TI)-2 Ab responses. Whereas T cell\u2013dependent Ab responses were only modestly increased in NOS2\u2212\/\u2212 mice, IgM and IgG3 Ab responses as well as marginal zone B cell plasma cell numbers and peritoneal B1b B cells were significantly elevated after immunization with the TI-2 Ag 4-hydroxy-3-nitrophenyl acetyl (NP)\u2013Ficoll. The elevated TI-2 responses in NOS2\u2212\/\u2212 mice were accompanied by significant increases in serum levels of BAFF\/BLyS and by increases in BAFF-producing Ly6Chi inflammatory monocytes and monocyte-derived dendritic cells (DCs), suggesting that NO normally inhibits BAFF expression. Indeed, we found that NOS2\u2212\/\u2212 DCs produced more BAFF than did wild-type DCs, and addition of a NO donor to NOS2\u2212\/\u2212 DCs reduced BAFF production. Bone marrow chimeric mice that lack NOS2 in either nonhematopoietic or hematopoietic cells had intermediate IgM and IgG3 Ab responses after NP-Ficoll immunization, suggesting that NOS2 from both hematopoietic and nonhematopoietic sources regulates TI-2 Ab responses. Similar to NOS2\u2212\/\u2212 mice, depletion of Ly6Chi inflammatory monocytes and monocyte-derived DCs enhanced NP-specific IgM and IgG3 responses to NP-Ficoll. Thus, NO produced by inflammatory monocytes and their derivative DC subsets plays an important role in regulating BAFF production and TI-2 Ab responses.<\/jats:p>","DOI":"10.4049\/jimmunol.1303158","type":"journal-article","created":{"date-parts":[[2014,6,21]],"date-time":"2014-06-21T08:05:10Z","timestamp":1403337910000},"page":"1110-1120","source":"Crossref","is-referenced-by-count":25,"title":["Nitric Oxide Regulates BAFF Expression and T Cell\u2013Independent Antibody Responses"],"prefix":"10.1093","volume":"193","author":[{"given":"Daniela","family":"Giordano","sequence":"first","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"}]},{"given":"Chang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias M","family":"Hohl","sequence":"additional","affiliation":[{"name":"Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A","family":"Clark","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Washington , Seattle, WA 98109"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,1]]},"reference":[{"key":"2025030707260820100_r1","doi-asserted-by":"crossref","first-page":"iii37","DOI":"10.1136\/ard.2006.058446","article-title":"Role of nitric oxide in the regulation of T cell functions","volume":"65","author":"Niedbala","year":"2006","journal-title":"Ann. 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