{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T00:16:16Z","timestamp":1790986576473,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2009,7,1]],"date-time":"2009-07-01T00:00:00Z","timestamp":1246406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Notch signaling pathway is one of the most conserved mechanisms to regulate cell fate in many tissues during development and postnatal life. In the immune system, Notch signaling regulates T and B cell development and modulates the differentiation of T and B cells. In this study, we investigated the functional roles of Notch signaling in human B cell differentiation within the germinal center (GC). Notch ligands, Delta-like 1 (Dll1) and Jagged 1 (Jg1), are expressed by follicular dendritic cells (FDC) but not by B cells in the GC, while GC-B cells express the Notch receptors, Notch1 and Notch2. The blockade of Notch signaling pathways using a \u03b3-secretase inhibitor, DAPT (N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester), reduces the survival of GC-B cells in the presence of FDC\/HK cells. Jg1 has a dominant effect on GC-B cell survival mediated by Notch signaling. Furthermore, Notch cooperates with another anti-apoptotic factor, BAFF\/Blys produced by FDC to support GC-B cell growth. Taken together, our data shows the important role of Notch signaling provided by FDC in the survival of GC-B cells in vitro.<\/jats:p>","DOI":"10.4049\/jimmunol.0803183","type":"journal-article","created":{"date-parts":[[2009,6,19]],"date-time":"2009-06-19T17:04:08Z","timestamp":1245431048000},"page":"352-358","source":"Crossref","is-referenced-by-count":62,"title":["Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis"],"prefix":"10.1093","volume":"183","author":[{"given":"Sun-Ok","family":"Yoon","sequence":"first","affiliation":[{"name":"Laboratory of Cellular Immunology, Ochsner Clinic Foundation , New Orleans, LA 70121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Immunology, Ochsner Clinic Foundation , New Orleans, LA 70121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Berner","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Immunology, Ochsner Clinic Foundation , New Orleans, LA 70121"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca","family":"Blom","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology of the Academic Medical Center, University of Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong Sung","family":"Choi","sequence":"additional","affiliation":[{"name":"Laboratory of Cellular Immunology, Ochsner Clinic Foundation , New Orleans, LA 70121"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2009,7,1]]},"reference":[{"key":"2026012811265864400_R1","first-page":"770","article-title":"Notch signaling: cell fate control and signal integration in development.","volume-title":"Science","year":"1999"},{"key":"2026012811265864400_R2","first-page":"945","article-title":"Regulation of lymphoid development, differentiation, and function by the Notch pathway.","volume-title":"Annu. Rev. Immunol.","year":"2005"},{"key":"2026012811265864400_R3","first-page":"135","article-title":"Notch signalling in B cells.","volume-title":"Semin. Cell. Dev. Biol.","year":"2003"},{"key":"2026012811265864400_R4","first-page":"443","article-title":"Notch-RBP-J signaling is involved in cell fate determination of marginal zone B cells.","volume-title":"Nat. Immunol.","year":"2002"},{"key":"2026012811265864400_R5","first-page":"675","article-title":"Notch2 is preferentially expressed in mature B cells and indispensable for marginal zone B lineage development.","volume-title":"Immunity","year":"2003"},{"key":"2026012811265864400_R6","first-page":"638","article-title":"Delta-like 1 is necessary for the generation of marginal zone B cells but not T cells in vivo.","volume-title":"Nat. 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Today","year":"1995"},{"key":"2026012811265864400_R12","first-page":"111","article-title":"Germinal center development.","volume-title":"Immunol. Rev.","year":"1997"},{"key":"2026012811265864400_R13","first-page":"764","article-title":"Are follicular dendritic cells really good for nothing?.","volume-title":"Nat. Rev. Immunol.","year":"2003"},{"key":"2026012811265864400_R14","first-page":"2","article-title":"How do follicular dendritic cells interact intimately with B cells in the germinal centre?.","volume-title":"Immunology","year":"2005"},{"key":"2026012811265864400_R15","first-page":"1006","article-title":"Cellular and molecular factors that regulate the differentiation and apoptosis of germinal center B cells.","volume-title":"J. Immunol.","year":"1996"},{"key":"2026012811265864400_R16","first-page":"49","article-title":"The distinct roles of T cell derived cytokines and a novel follicular dendritic cell-signaling molecule 8D6 in germinal center-B cell differentiation.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012811265864400_R17","first-page":"929","article-title":"Mechanism of antigen-driven selection in germinal centers.","volume-title":"Nature","year":"1989"},{"key":"2026012811265864400_R18","first-page":"2368","article-title":"Suppression of apoptosis in normal and neoplastic human B lymphocytes by CD40 ligand is independent of Bc1\u20132 induction.","volume-title":"Eur. J. Immunol.","year":"1993"},{"key":"2026012811265864400_R19","first-page":"1985","article-title":"Follicular dendritic cells inhibit apoptosis in human B lymphocytes by a rapid and irreversible blockade of preexisting endonuclease.","volume-title":"J. Exp. Med.","year":"1995"},{"key":"2026012811265864400_R20","first-page":"1101","article-title":"Stimulation of germinal center B lymphocyte proliferation by an FDC-like cell line, HK.","volume-title":"J. Immunol.","year":"1995"},{"key":"2026012811265864400_R21","first-page":"6473","article-title":"Cutting edge: cellular Fas-associated death domain-like IL-1-converting enzyme-inhibitory protein protects germinal center B cells from apoptosis during germinal center reactions.","volume-title":"J. Immunol.","year":"2001"},{"key":"2026012811265864400_R22","first-page":"2951","article-title":"Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes.","volume-title":"J. Immunol.","year":"1994"},{"key":"2026012811265864400_R23","first-page":"508","article-title":"Interleukin-10 interrupts memory B cell expansion in the germinal center by inducing differentiation into plasma.","volume-title":"Eur. J. Immunol.","year":"1998"},{"key":"2026012811265864400_R24","first-page":"2446","article-title":"Delta-like1-induced Notch1 signaling regulates the human plasmacytoid dendritic cell versus T-cell lineage decision through control of GATA-3 and Spi-B.","volume-title":"Blood","year":"2006"},{"key":"2026012811265864400_R25","first-page":"133","article-title":"Interleukin-12 stimulates B cell growth by inducing IFN-\u03b3.","volume-title":"Cell. Immunol.","year":"1996"},{"key":"2026012811265864400_R26","first-page":"1695","article-title":"Altered Notch ligand expression in human liver disease: further evidence for a role of the Notch signaling pathway in hepatic neovascularization and biliary ductular defects.","volume-title":"Am. J. 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Med.","year":"2000"},{"key":"2026012811265864400_R31","first-page":"2847","article-title":"Monocytes express high amounts of Notch and undergo cytokine specific apoptosis following interaction with the Notch ligand, Delta-1.","volume-title":"Blood","year":"2000"},{"key":"2026012811265864400_R32","first-page":"3757","article-title":"The functional role of B cell antigen receptor stimulation and IL-4 in the generation of human memory B cells from germinal center B cells.","volume-title":"J. Immunol.","year":"1997"},{"key":"2026012811265864400_R33","first-page":"688","article-title":"A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish.","volume-title":"EMBO Rep.","year":"2002"},{"key":"2026012811265864400_R34","first-page":"8180","article-title":"Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells.","volume-title":"J. 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