Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis

Notch Ligands Expressed by Follicular Dendritic Cells Protect Germinal Center B Cells from Apoptosis
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滤泡树突状细胞表达的 Notch 配体可保护生发中心 B 细胞免于凋亡

DOI:
10.4049/jimmunol.0803183
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发表时间:
2009
期刊:
The Journal of Immunology
影响因子:
--
通讯作者:
Y. Choi
Y. Choi
中科院分区:
--
文献类型:
--
作者:
Sun;Xin Zhang;P. Berner;B. Blom;Y. Choi

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Notch信号通路是许多组织发育和出生后生命中调控细胞命运的最保守的机制之一。在免疫系统中,Notch信号调节T和B细胞的发育,并调节T和B细胞的分化。在这项研究中,我们研究了Notch信号在生发中心(GC)内人类B细胞分化中的功能作用。Notch配体Delta-like 1(DLL1)和Jg1(JG1)由滤泡树突状细胞(FDC)表达,而GC-B细胞表达Notch受体Notch1和Notch2。DAPT(N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycine叔丁酯(DAPTγ叔丁酯)阻断Notch信号通路,降低GC-B细胞在FDC/HK细胞存在下的存活率。JG1对Notch信号介导的GC-B细胞存活具有显性作用。此外,Notch与FDC产生的另一种抗凋亡因子BAFF/BLyS合作,以支持GC-B细胞的生长。综上所述,我们的数据显示了FDC提供的Notch信号在GC-B细胞体外存活中的重要作用。
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 γ-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.
DOI: 10.4049/jimmunol.153.7.2951
发表时间: 1994-10
影响因子: 4.4
作者:
Han Soo Kim;Xinhong Zhang;Y. Choi
通讯作者: Han Soo Kim;Xinhong Zhang;Y. Choi
DOI: 10.1182/blood.v95.9.2847.009k19_2847_2854
发表时间: 2000-05-01
期刊: BLOOD
影响因子: 20.3
作者:
Ohishi, K;Varnum-Finney, B;Bernstein, ID
通讯作者: Bernstein, ID
FDC 样细胞系 HK 刺激生发中心 B 淋巴细胞增殖。
DOI: --
发表时间: 1995
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Kim,HS;Zhang,X;Klyushnenkova,E;Choi,YS
通讯作者: Choi,YS