{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:45:33Z","timestamp":1791287133180,"version":"4.1.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,5,1]],"date-time":"2015-05-01T00:00:00Z","timestamp":1430438400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The B cell-activating factor (BAFF) is critical for B cell development and humoral immunity in mice and humans. While the role of BAFF in B cells has been widely described, its role in innate immunity remains unknown. Using BAFF receptor (BAFFR)-deficient mice, we characterized BAFFR-related innate and adaptive immune functions following infection with vesicular stomatitis virus (VSV) and lymphocytic choriomeningitis virus (LCMV). We identified a critical role for BAFFR signaling in the generation and maintenance of the CD169\n            <jats:sup>+<\/jats:sup>\n            macrophage compartment. Consequently,\n            <jats:italic>Baffr<\/jats:italic>\n            <jats:sup>\u2212<\/jats:sup>\n            <jats:sup>\n              <jats:italic>\/<\/jats:italic>\n            <\/jats:sup>\n            <jats:sup>\u2212<\/jats:sup>\n            mice exhibited limited induction of innate type I interferon production after viral infection. Lack of BAFFR signaling reduced virus amplification and presentation following viral infection, resulting in highly reduced antiviral adaptive immune responses. As a consequence, BAFFR-deficient mice showed exacerbated and fatal disease after viral infection. Mechanistically, transient lack of B cells in\n            <jats:italic>Baffr<\/jats:italic>\n            <jats:sup>\u2212<\/jats:sup>\n            <jats:sup>\n              <jats:italic>\/<\/jats:italic>\n            <\/jats:sup>\n            <jats:sup>\u2212<\/jats:sup>\n            animals resulted in limited lymphotoxin expression, which is critical for maintenance of CD169\n            <jats:sup>+<\/jats:sup>\n            cells. In conclusion, BAFFR signaling affects both innate and adaptive immune activation during viral infections.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Viruses cause acute and chronic infections in humans resulting in millions of deaths every year. Innate immunity is critical for the outcome of a viral infection. Innate type I interferon production can limit viral replication, while adaptive immune priming by innate immune cells induces pathogen-specific immunity with long-term protection. Here, we show that BAFFR deficiency not only perturbed B cells, but also resulted in limited CD169\n            <jats:sup>+<\/jats:sup>\n            macrophages. These macrophages are critical in amplifying viral particles to trigger type I interferon production and initiate adaptive immune priming. Consequently, BAFFR deficiency resulted in reduced enforced viral replication, limited type I interferon production, and reduced adaptive immunity compared to BAFFR-competent controls. As a result, BAFFR-deficient mice were predisposed to fatal viral infections. Thus, BAFFR expression is critical for innate immune activation and antiviral immunity.\n          <\/jats:p>","DOI":"10.1128\/jvi.02976-14","type":"journal-article","created":{"date-parts":[[2015,2,12]],"date-time":"2015-02-12T06:52:40Z","timestamp":1423723960000},"page":"4748-4759","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":27,"title":["Deficiency of the B Cell-Activating Factor Receptor Results in Limited CD169\n            <sup>+<\/sup>\n            Macrophage Function during Viral Infection"],"prefix":"10.1128","volume":"89","author":[{"given":"Haifeng C.","family":"Xu","sequence":"first","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada"},{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal","family":"Khairnar","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vikas","family":"Duhan","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra A.","family":"Pandyra","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Grusdat","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashant","family":"Shinde","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"McIlwain","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Baxter Laboratory in Stem Cell Biology, Department of Microbiology and Immunology, Stanford University, Stanford, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sathish Kumar","family":"Maney","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Gommerman","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Toronto, Toronto, Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"L\u00f6hning","sequence":"additional","affiliation":[{"name":"Experimental Immunology, Department of Rheumatology and Clinical Immunology, Charit\u00e9 University Medicine Berlin, Berlin, Germany"},{"name":"German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela S.","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada"},{"name":"Department of Immunology, University of Toronto, Toronto, Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tak W.","family":"Mak","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada"},{"name":"Department of Immunology, University of Toronto, Toronto, Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Pieper","sequence":"additional","affiliation":[{"name":"University Medical Centre Freiburg, Center of Chronic Immunodeficiency Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heiko","family":"Sic","sequence":"additional","affiliation":[{"name":"University Medical Centre Freiburg, Center of Chronic Immunodeficiency Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthaios","family":"Speletas","sequence":"additional","affiliation":[{"name":"Department of Immunology and Histocompatibility, Faculty of Medicine, University of Thessaly, Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Eibel","sequence":"additional","affiliation":[{"name":"University Medical Centre Freiburg, Center of Chronic Immunodeficiency Freiburg, Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl F.","family":"Ware","sequence":"additional","affiliation":[{"name":"Sanford Burnham Medical Research Institute, La Jolla, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexei V.","family":"Tumanov","sequence":"additional","affiliation":[{"name":"Trudeau Institute, Saranac Lake, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey A.","family":"Kruglov","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergei A.","family":"Nedospasov","sequence":"additional","affiliation":[{"name":"German Rheumatism Research Center (DRFZ), Leibniz Institute, Berlin, Germany"},{"name":"Lomonosov Moscow State University, Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dieter","family":"H\u00e4ussinger","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike","family":"Recher","sequence":"additional","affiliation":[{"name":"Primary Immunodeficiency Clinic, Medical Outpatient Division and Immunodeficiency Laboratory, Department of Biomedicine, University Hospital Basel, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl S.","family":"Lang","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Essen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Campell Family Institute for Breast Cancer Research, Princess Margaret Cancer Centre, University Health Network (UHN), Toronto, Ontario, Canada"},{"name":"Department of Gastroenterology, Hepatology and Infectious Diseases, University of D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Department of Molecular Medicine II, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061964"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1061965"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903543106"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.4.2245"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2572"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2008.01.009"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403286200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni842"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.04.005"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1157340"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1678"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060990"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051283"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805460105"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.11.015"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2414"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1669"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature06287"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.imlet.2006.04.004"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.76.5.2375-2383.2002"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2169"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.1.261"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80461-6"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/smim.2000.0253"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/88678"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20030684"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1002106"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2194"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00397-7"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8009221"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2012.167"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.11.5739"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2014.05.004"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1117729"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1002712"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003999"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI31990"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(00)80588-9"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2012.01.013"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.6.3620"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12251"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200626255"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.04.008"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38010"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI45563"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)61354-2"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1111\/imr.12091"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2527"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003650"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni911"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e3282f0ad25"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(01)00222-9"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2007.12.008"}],"container-title":["Journal of Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02976-14","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/JVI.02976-14","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T15:56:32Z","timestamp":1646495792000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/JVI.02976-14"}},"subtitle":[],"editor":[{"given":"B.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2015,5]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1128\/JVI.02976-14"],"URL":"https:\/\/doi.org\/10.1128\/jvi.02976-14","relation":{},"ISSN":["0022-538X","1098-5514"],"issn-type":[{"value":"0022-538X","type":"print"},{"value":"1098-5514","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,5]]},"assertion":[{"value":"2014-10-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-02-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2015-04-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}