{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:35:31Z","timestamp":1773286531071,"version":"3.50.1"},"reference-count":66,"publisher":"Rockefeller University Press","issue":"10","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,11,17]]},"abstract":"<jats:p>Extensive studies of mice deficient in one or several cytokine receptors have failed to support an indispensable role of cytokines in development of multiple blood cell lineages. Whereas B1 B cells and Igs are sustained at normal levels throughout life of mice deficient in IL-7, IL-7R\u03b1, common cytokine receptor gamma chain, or flt3 ligand (FL), we report here that adult mice double deficient in IL-7R\u03b1 and FL completely lack visible LNs, conventional IgM+ B cells, IgA+ plasma cells, and B1 cells, and consequently produce no Igs. All stages of committed B cell progenitors are undetectable in FL\u2212\/\u2212 \u00d7 IL-7R\u03b1\u2212\/\u2212 BM that also lacks expression of the B cell commitment factor Pax5 and its direct target genes. Furthermore, in contrast to IL-7R\u03b1\u2212\/\u2212 mice, FL\u2212\/\u2212 \u00d7 IL-7R\u03b1\u2212\/\u2212 mice also lack mature B cells and detectable committed B cell progenitors during fetal development. Thus, signaling through the cytokine tyrosine kinase receptor flt3 and IL-7R\u03b1 are indispensable for fetal and adult B cell development.<\/jats:p>","DOI":"10.1084\/jem.20031152","type":"journal-article","created":{"date-parts":[[2003,11,11]],"date-time":"2003-11-11T01:24:21Z","timestamp":1068513861000},"page":"1495-1506","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":136,"title":["Complementary Signaling through flt3 and Interleukin-7 Receptor \u03b1 Is Indispensable for Fetal and Adult B Cell Genesis"],"prefix":"10.1084","volume":"198","author":[{"given":"Ewa","family":"Sitnicka","sequence":"first","affiliation":[{"name":"1Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, SE-221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cord","family":"Brakebusch","sequence":"additional","affiliation":[{"name":"2Max Planck Institute of Biochemistry, 82152 Martinsried, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga-Lill","family":"Martensson","sequence":"additional","affiliation":[{"name":"3Developmental Immunology, Babraham Institute, CB2 4AT Cambridge, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"Svensson","sequence":"additional","affiliation":[{"name":"4Immunology Section, Department of Cell and Molecular Biology, University of Lund, 221 00 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William W.","family":"Agace","sequence":"additional","affiliation":[{"name":"4Immunology Section, Department of Cell and Molecular Biology, University of Lund, 221 00 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mikael","family":"Sigvardsson","sequence":"additional","affiliation":[{"name":"1Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, SE-221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalija","family":"Buza-Vidas","sequence":"additional","affiliation":[{"name":"1Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, SE-221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Bryder","sequence":"additional","affiliation":[{"name":"1Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, SE-221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corrado","family":"M.Cilio","sequence":"additional","affiliation":[{"name":"5Department of Paediatrics and Department of Endocrinology, Malmo\u0308 University Hospital, SE 205 02 Malmo\u0308, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henrik","family":"Ahlenius","sequence":"additional","affiliation":[{"name":"1Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, SE-221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eugene","family":"Maraskovsky","sequence":"additional","affiliation":[{"name":"6Ludwig Institute for Cancer Research, Heidelberg, Victoria, 3084, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques J.","family":"Peschon","sequence":"additional","affiliation":[{"name":"7Amgen Corporation, Seattle, WA 98101"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sten Eirik W.","family":"Jacobsen","sequence":"additional","affiliation":[{"name":"1Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology and Cell Therapy, Lund University Hospital, SE-221 84 Lund, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"291","published-online":{"date-parts":[[2003,11,10]]},"reference":[{"key":"2023072511585419700_BIB1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1146\/annurev.cb.11.110195.000343","volume":"11","year":"1995","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2023072511585419700_BIB2","doi-asserted-by":"crossref","first-page":"2844","DOI":"10.1182\/blood.V81.11.2844.2844","volume":"81","year":"1993","journal-title":"Blood."},{"key":"2023072511585419700_BIB3","doi-asserted-by":"crossref","first-page":"3515","DOI":"10.1182\/blood.V82.12.3515.3515","volume":"82","year":"1993","journal-title":"Blood."},{"key":"2023072511585419700_BIB4","doi-asserted-by":"crossref","first-page":"3295","DOI":"10.1038\/sj.onc.1205318","volume":"21","year":"2002","journal-title":"Oncogene."},{"key":"2023072511585419700_BIB5","doi-asserted-by":"crossref","first-page":"3284","DOI":"10.1038\/sj.onc.1205319","volume":"21","year":"2002","journal-title":"Oncogene."},{"key":"2023072511585419700_BIB6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1038\/352621a0","volume":"352","year":"1991","journal-title":"Nature."},{"key":"2023072511585419700_BIB7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1038\/32190","volume":"392","year":"1998","journal-title":"Nature."},{"key":"2023072511585419700_BIB8","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.1948049","volume":"254","year":"1991","journal-title":"Science."},{"key":"2023072511585419700_BIB9","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1084\/jem.181.4.1519","volume":"181","year":"1995","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB10","doi-asserted-by":"crossref","first-page":"5592","DOI":"10.1073\/pnas.91.12.5592","volume":"91","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511585419700_BIB11","doi-asserted-by":"crossref","first-page":"1737","DOI":"10.1182\/blood.V84.6.1737.1737","volume":"84","year":"1994","journal-title":"Blood."},{"key":"2023072511585419700_BIB12","doi-asserted-by":"crossref","first-page":"3423","DOI":"10.1182\/blood.V90.9.3423","volume":"90","year":"1997","journal-title":"Blood."},{"key":"2023072511585419700_BIB13","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1126\/science.8073287","volume":"265","year":"1994","journal-title":"Science."},{"key":"2023072511585419700_BIB14","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1182\/blood.V99.10.3573","volume":"99","year":"2002","journal-title":"Blood."},{"key":"2023072511585419700_BIB15","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1182\/blood.V91.8.2745.2745_2745_2752","volume":"91","year":"1998","journal-title":"Blood."},{"key":"2023072511585419700_BIB16","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1182\/blood.V95.2.528","volume":"95","year":"2000","journal-title":"Blood."},{"key":"2023072511585419700_BIB17","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1002\/stem.5530160706","volume":"16","year":"1998","journal-title":"Stem Cells."},{"key":"2023072511585419700_BIB18","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1016\/S0301-472X(00)00504-X","volume":"28","year":"2000","journal-title":"Exp. Hematol."},{"key":"2023072511585419700_BIB19","doi-asserted-by":"crossref","first-page":"2583","DOI":"10.1182\/blood.V90.7.2583","volume":"90","year":"1997","journal-title":"Blood."},{"key":"2023072511585419700_BIB20","doi-asserted-by":"crossref","first-page":"3037","DOI":"10.1182\/blood.V90.8.3037","volume":"90","year":"1997","journal-title":"Blood."},{"key":"2023072511585419700_BIB21","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1182\/blood.V97.4.922","volume":"97","year":"2001","journal-title":"Blood."},{"key":"2023072511585419700_BIB22","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/1074-7613(95)90046-2","volume":"2","year":"1995","journal-title":"Immunity."},{"key":"2023072511585419700_BIB23","doi-asserted-by":"crossref","first-page":"9565","DOI":"10.1073\/pnas.92.21.9565","volume":"92","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511585419700_BIB24","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1182\/blood.V88.7.2458.bloodjournal8872458","volume":"88","year":"1996","journal-title":"Blood."},{"key":"2023072511585419700_BIB25","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0952-7915(03)00012-8","volume":"15","year":"2003","journal-title":"Curr. Opin. Immunol."},{"key":"2023072511585419700_BIB26","doi-asserted-by":"crossref","first-page":"1955","DOI":"10.1084\/jem.180.5.1955","volume":"180","year":"1994","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB27","doi-asserted-by":"crossref","first-page":"7172","DOI":"10.1073\/pnas.93.14.7172","volume":"93","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511585419700_BIB28","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1084\/jem.194.8.1141","volume":"194","year":"2001","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB29","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1084\/jem.20020784","volume":"196","year":"2002","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB30","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1093\/intimm\/10.9.1367","volume":"10","year":"1998","journal-title":"Int. Immunol."},{"key":"2023072511585419700_BIB31","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/1074-7613(95)90047-0","volume":"2","year":"1995","journal-title":"Immunity."},{"key":"2023072511585419700_BIB32","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1073\/pnas.92.2.377","volume":"92","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"2023072511585419700_BIB33","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0092-8674(94)90333-6","volume":"76","year":"1994","journal-title":"Cell."},{"key":"2023072511585419700_BIB34","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1182\/blood.V91.4.1101","volume":"91","year":"1998","journal-title":"Blood."},{"key":"2023072511585419700_BIB35","doi-asserted-by":"crossref","first-page":"644","DOI":"10.4049\/jimmunol.155.2.644","volume":"155","year":"1995","journal-title":"J. Immunol."},{"key":"2023072511585419700_BIB36","doi-asserted-by":"crossref","first-page":"3489","DOI":"10.1182\/blood.V95.11.3489","volume":"95","year":"2000","journal-title":"Blood."},{"key":"2023072511585419700_BIB37","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1074-7613(02)00419-3","volume":"17","year":"2002","journal-title":"Immunity."},{"key":"2023072511585419700_BIB38","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/1074-7613(95)90167-1","volume":"3","year":"1995","journal-title":"Immunity."},{"key":"2023072511585419700_BIB39","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1182\/blood.V88.4.1256.bloodjournal8841256","volume":"88","year":"1996","journal-title":"Blood."},{"key":"2023072511585419700_BIB40","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1002\/eji.1830201006","volume":"20","year":"1990","journal-title":"Eur. J. Immunol."},{"key":"2023072511585419700_BIB41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1172\/JCI0215988","volume":"110","year":"2002","journal-title":"J. Clin. Invest."},{"key":"2023072511585419700_BIB42","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/0019-2791(71)90454-X","volume":"8","year":"1971","journal-title":"Immunochemistry."},{"key":"2023072511585419700_BIB43","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1084\/jem.173.3.711","volume":"173","year":"1991","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/intimm\/10.1.1","volume":"10","year":"1998","journal-title":"Int. Immunol."},{"key":"2023072511585419700_BIB45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1084\/jem.183.1.187","volume":"183","year":"1996","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB46","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/S1286-4579(01)01460-5","volume":"3","year":"2001","journal-title":"Microbes Infect."},{"key":"2023072511585419700_BIB47","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.4049\/jimmunol.168.9.4257","volume":"168","year":"2002","journal-title":"J. Immunol."},{"key":"2023072511585419700_BIB48","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0952-7915(00)00204-1","volume":"13","year":"2001","journal-title":"Curr. Opin. Immunol."},{"key":"2023072511585419700_BIB49","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1084\/jem.173.5.1213","volume":"173","year":"1991","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB50","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/S1074-7613(00)80268-X","volume":"5","year":"1996","journal-title":"Immunity."},{"key":"2023072511585419700_BIB51","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/S0952-7915(02)00324-2","volume":"14","year":"2002","journal-title":"Curr. Opin. Immunol."},{"key":"2023072511585419700_BIB52","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1101\/gad.6.9.1589","volume":"6","year":"1992","journal-title":"Genes Dev."},{"key":"2023072511585419700_BIB53","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/0092-8674(94)90079-5","volume":"79","year":"1994","journal-title":"Cell."},{"key":"2023072511585419700_BIB54","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/44076","volume":"401","year":"1999","journal-title":"Nature."},{"key":"2023072511585419700_BIB55","first-page":"2662","volume":"12","year":"1992","journal-title":"Mol. Cell. Biol."},{"key":"2023072511585419700_BIB56","doi-asserted-by":"crossref","first-page":"2198","DOI":"10.1101\/gad.10.17.2198","volume":"10","year":"1996","journal-title":"Genes Dev."},{"key":"2023072511585419700_BIB57","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1101\/gad.11.4.476","volume":"11","year":"1997","journal-title":"Genes Dev."},{"key":"2023072511585419700_BIB58","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1093\/emboj\/17.8.2319","volume":"17","year":"1998","journal-title":"EMBO J."},{"key":"2023072511585419700_BIB59","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/stem.140369","volume":"14","year":"1996","journal-title":"Stem Cells."},{"key":"2023072511585419700_BIB60","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1084\/jem.192.5.659","volume":"192","year":"2000","journal-title":"J. Exp. Med."},{"key":"2023072511585419700_BIB61","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1126\/science.1067518","volume":"297","year":"2002","journal-title":"Science."},{"key":"2023072511585419700_BIB62","doi-asserted-by":"crossref","first-page":"4926","DOI":"10.4049\/jimmunol.170.10.4926","volume":"170","year":"2003","journal-title":"J. Immunol."},{"key":"2023072511585419700_BIB63","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1016\/S1074-7613(01)00220-5","volume":"15","year":"2001","journal-title":"Immunity."},{"key":"2023072511585419700_BIB64","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S1074-7613(00)80329-5","volume":"6","year":"1997","journal-title":"Immunity."},{"key":"2023072511585419700_BIB65","doi-asserted-by":"crossref","first-page":"3892","DOI":"10.1182\/blood.V99.11.3892","volume":"99","year":"2002","journal-title":"Blood."},{"key":"2023072511585419700_BIB66","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/intimm\/10.3.325","volume":"10","year":"1998","journal-title":"Int. Immunol."}],"container-title":["The Journal of Experimental Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/198\/10\/1495\/1709820\/jem198101495.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jem\/article-pdf\/198\/10\/1495\/1709820\/jem198101495.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T11:59:47Z","timestamp":1690286387000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jem\/article\/198\/10\/1495\/39856\/Complementary-Signaling-through-flt3-and"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,11,10]]},"references-count":66,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2003,11,17]]}},"URL":"https:\/\/doi.org\/10.1084\/jem.20031152","relation":{},"ISSN":["1540-9538","0022-1007"],"issn-type":[{"value":"1540-9538","type":"electronic"},{"value":"0022-1007","type":"print"}],"subject":[],"published":{"date-parts":[[2003,11,10]]}}}