{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:37:10Z","timestamp":1791214630840,"version":"4.1.0"},"reference-count":42,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2010,3,9]]},"abstract":"<jats:p>\n                    IFN-regulatory factor 5 (IRF-5), a member of the IRF family, is a transcription factor that has a key role in the induction of the antiviral and inflammatory response. When compared with C57BL\/6 mice,\n                    <jats:italic>\n                      Irf5\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice show higher susceptibility to viral infection and decreased serum levels of type I IFN and the inflammatory cytokines IL-6 and TNF-\u03b1. Here, we demonstrate that IRF-5 is involved in B-cell maturation and the stimulation of Blimp-1 expression. The\n                    <jats:italic>\n                      Irf5\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice develop an age-related splenomegaly, associated with a dramatic accumulation of CD19\n                    <jats:sup>+<\/jats:sup>\n                    B220\n                    <jats:sup>\u2212<\/jats:sup>\n                    B cells and a disruption of normal splenic architecture. Splenic B cells from\n                    <jats:italic>\n                      Irf5\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice also exhibited a decreased level of plasma cells. The CD19\n                    <jats:sup>+<\/jats:sup>\n                    <jats:italic>\n                      Irf5\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    B cells show a defect in Toll-like receptor (TLR) 7- and TLR9-induced IL-6 production, and the aged\n                    <jats:italic>\n                      Irf5\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice have decreased serum levels of natural antibodies; however, the antigen-specific IgG1 primary response was already dependent in IRF-5 in young mice, although the IgM response was not. Analysis of the profile of transcription factors associated with plasma cell differentiation shows down-regulation of Blimp-1 expression, a master regulator of plasma cell differentiation, which can be reconstituted with ectopic IRF-5. IRF-5 stimulates transcription of the\n                    <jats:italic>Prdm1<\/jats:italic>\n                    gene encoding Blimp-1 and binds to the IRF site in the\n                    <jats:italic>Prdm1<\/jats:italic>\n                    promoter. Collectively, these results reveal that the age-related splenomegaly in\n                    <jats:italic>\n                      Irf5\n                      <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    <\/jats:italic>\n                    mice is associated with an accumulation of CD19\n                    <jats:sup>+<\/jats:sup>\n                    B220\n                    <jats:sup>\u2212<\/jats:sup>\n                    B cells with impaired functions and show the role of IRF-5 in the direct regulation of the plasma cell commitment factor Blimp-1 and in B-cell terminal differentiation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0911193107","type":"journal-article","created":{"date-parts":[[2010,2,22]],"date-time":"2010-02-22T22:35:31Z","timestamp":1266878131000},"page":"4664-4668","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":102,"title":["Critical role of IRF-5 in regulation of B-cell differentiation"],"prefix":"10.1073","volume":"107","author":[{"given":"Chunyang","family":"Lien","sequence":"first","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and Departments of"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chee-Mun","family":"Fang","sequence":"additional","affiliation":[{"name":"Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Huso","sequence":"additional","affiliation":[{"name":"Comparative Medicine, The Johns Hopkins University, Baltimore, MD, 21218;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"Livak","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runqing","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Genetics, Cell Biology and Anatomy, Nebraska Medical Center, Omaha, NE 68198"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula M.","family":"Pitha","sequence":"additional","affiliation":[{"name":"The Sidney Kimmel Comprehensive Cancer Center and Departments of"},{"name":"Biology and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2010,3,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2007.01.014"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.623"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03308"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M800501200"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500543200"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0701266104"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/428480"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.192.2.271"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060411"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2007.02.002"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.01.012"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2007.04.007"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(02)00335-7"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20080526"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/eji.1830260142"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2006.07.009"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/28.24.4846"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1104803"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-01-129049"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.08.011"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1357"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01946-07"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20051450"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature04267"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5124"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0803706"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90321-2"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.23.8684-8695.2000"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2217"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20042060"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175870"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508327102"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.7.4343"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.9.5556"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.5.5.868"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.2.1158"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03147"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20062041"},{"key":"e_1_3_3_39_2","first-page":"6424","article-title":"Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death","volume":"63","author":"Barnes BJ","year":"2003","unstructured":"BJ Barnes, MJ Kellum, KE Pinder, JA Frisancho, PM Pitha, Interferon regulatory factor 5, a novel mediator of cell cycle arrest and cell death. Cancer Res 63, 6424\u20136431 (2003).","journal-title":"Cancer Res"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0005500"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M809252200"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7898"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0911193107","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T19:09:24Z","timestamp":1649790564000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0911193107"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,3,9]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2010,3,9]]}},"alternative-id":["10.1073\/pnas.0911193107"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0911193107","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2010,3,9]]},"assertion":[{"value":"2010-03-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}