{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:07:34Z","timestamp":1785326854392,"version":"3.55.0"},"reference-count":33,"publisher":"National Academy of Sciences","issue":"11","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,17]]},"abstract":"\n Francisella tularensis<\/jats:italic>\n (\n Ft<\/jats:italic>\n ), a Gram-negative intracellular bacterium, is the etiologic agent of tularemia. Infection of mice with <10\n Ft<\/jats:italic>\n Live Vaccine Strain (\n Ft<\/jats:italic>\n LVS) organisms i.p. causes a lethal infection that resembles human tularemia. Here, we show that immunization with as little as 0.1 ng\n Ft<\/jats:italic>\n LVS lipopolysaccharide (\n Ft<\/jats:italic>\n -LPS), but not\n Ft<\/jats:italic>\n lipid A, generates a rapid antibody response that protects wild-type (WT) mice against lethal\n Ft<\/jats:italic>\n LVS challenge. Protection is not induced in\n Ft<\/jats:italic>\n -LPS-immunized B cell-deficient mice (\u03bcMT or JhD), male\n xid<\/jats:italic>\n mice, or Ig transgenic mice that produce a single IgH (not reactive with\n Ft<\/jats:italic>\n -LPS). Focusing on the cellular mechanisms that underlie this protective response, we show that\n Ft<\/jats:italic>\n -LPS specifically stimulates proliferation of B-1a lymphocytes that bind fluorochrome-labeled\n Ft<\/jats:italic>\n -LPS and the differentiation of these cells to plasma cells that secrete antibodies specific for\n Ft<\/jats:italic>\n -LPS. This exclusively B-1a antibody response is equivalent in WT, T-deficient (TCR\u03b1\u03b2\n \u2212\/\u2212<\/jats:sup>\n , TCR\u03b3\u03b4\n \u2212\/\u2212<\/jats:sup>\n ), and Toll-like receptor 4 (TLR4)-deficient (TLR4\n \u2212\/\u2212<\/jats:sup>\n ) mice and thus is not dependent on T cells or typical inflammatory processes. Serum antibody levels peak \u22485 days after\n Ft<\/jats:italic>\n -LPS immunization and persist at low levels for months. Thus, immunization with\n Ft<\/jats:italic>\n -LPS activates a rare population of antigen-specific B-1a cells to produce a persistent T-independent antibody response that provides long-term protection against lethal\n Ft<\/jats:italic>\n LVS infection. These data support the possibility of creating effective, minimally invasive vaccines that can provide effective protection against pathogen invasion.\n <\/jats:p>","DOI":"10.1073\/pnas.0813411106","type":"journal-article","created":{"date-parts":[[2009,2,26]],"date-time":"2009-02-26T21:45:45Z","timestamp":1235684745000},"page":"4343-4348","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":101,"title":["Antigen-specific B-1a antibodies induced by\n Francisella tularensis<\/i>\n LPS provide long-term protection against\n F. tularensis<\/i>\n LVS challenge"],"prefix":"10.1073","volume":"106","author":[{"given":"Leah E.","family":"Cole","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L.","family":"Elkins","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ellen T.","family":"Fernandez","sequence":"additional","affiliation":[{"name":"Laboratory of Mycobacterial Diseases and Cellular Immunology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20852;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilofer","family":"Qureshi","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Science, University of Missouri, Kansas City, MO 64108; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Shlomchik","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Immunobiology, Yale University School of Medicine, New Haven, CT 06520-8035"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonard A.","family":"Herzenberg","sequence":"additional","affiliation":[{"name":"Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonore A.","family":"Herzenberg","sequence":"additional","affiliation":[{"name":"Department of Genetics, School of Medicine, Stanford University, Stanford, CA 94305;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie N.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland, Baltimore, MD 21201;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2763"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1286-4579(02)00084-9"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-07-0182"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-004-0182-2"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.4.1319"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/2.6.515"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.11.6888"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.1988-1996.2000"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/5.6.647"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.7.931"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V94.7.2357.419k40_2357_2364"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/1074-7613(95)90114-0"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8332901"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(01)00189-X"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/0008-8749(87)90071-2"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830141212"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"2574","DOI":"10.4049\/jimmunol.130.6.2574","article-title":"Contribution of Lyb 5+ and Lyb 5- B cells to the primary and secondary phosphocholine-specific antibody response","volume":"130","author":"Kenny JJ","year":"1983","unstructured":"JJ Kenny, LJ Yaffe, A Ahmed, ES Metcalf, Contribution of Lyb 5+ and Lyb 5- B cells to the primary and secondary phosphocholine-specific antibody response. 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