CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway.
CD40 ligation induces Apo-1/Fas expression on human B lymphocytes and facilitates apoptosis through the Apo-1/Fas pathway.
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CD40连接诱导人B淋巴细胞上的APO-1/FAS表达，并通过APO-1/FAS途径促进凋亡。
DOI：
10.1084/jem.182.5.1557
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发表时间：
1995-11-01
影响因子：
15.3
通讯作者：
Friedman, Steven M.
中科院分区：
文献类型：
--
作者：
Schattner, Elaine J.;Elkon, Keith B.;Yoo, Dae-Hyun;Tumang, Joseph;Krammer, Peter H.;Crow, Mary K.;Friedman, Steven M.
当与Fas配体或抗Apo-1/Fas抗体结合时，Apo-1/Fas抗原（CD 95）介导淋巴细胞的程序性细胞死亡。相反，当CD 40抗原被其T细胞配体（CD 40 L，gp 39）接合或被抗CD 40抗体交联时，其向B淋巴细胞提供有效的活化和存活信号。本研究以人扁桃体B细胞和拉莫斯Burkitt淋巴瘤B细胞系（作为人生殖中心B淋巴细胞的模型）为研究对象，探讨Apo-1/Fas表达和人B细胞凋亡的影响因素。我们发现，在通过（a）由微生物超抗原（SAg）介导的同源T辅助细胞-B细胞相互作用;（B）与CD 40 L+而不是CD 40 L-Jurkat突变T细胞克隆的接触依赖性相互作用;和（c）单克隆抗CD 40而不是一组对照抗体中的任何一种诱导的CD 40连接后，恶性和正常人B淋巴细胞上的Apo-1/Fas表达上调。增强的B细胞Fas/Apo-1表达具有功能意义。拉莫斯伯基特淋巴瘤系细胞与经辐照的SAg反应性CD 4 + T细胞和SAg或CD 40 L + Jurkat T细胞的共培养导致B细胞凋亡，这通过降低的细胞活力和DNA梯状化来证明。通过添加抗Apo-1/Fas单克隆抗体增强该过程，这与获得性对Apo-1/Fas介导的凋亡的易感性一致。这些数据支持一种免疫调节途径，其中涉及B细胞增殖/存活抗原CD 40以及介导淋巴细胞程序性细胞死亡的Apo-1/Fas分子的看似矛盾的信号在人B细胞活化过程中相关联。
The Apo-1/Fas antigen (CD95) mediates programmed cell death of lymphocytes when bound by Fas ligand or anti-Apo-1/Fas antibody. In contrast, the CD40 antigen provides a potent activation and survival signal to B lymphocytes when it is engaged by its T cell ligand (CD40L, gp39) or cross-linked by anti-CD40 antibody. In this study, we use human tonsillar B cells and the Ramos Burkitt's lymphoma B cell line, which serves as a model for human germinal center B lymphocytes, to study the effectors of Apo-1/Fas expression and apoptosis of human B cells. We found that Apo-1/Fas expression was upregulated on both malignant and normal human B lymphocytes after CD40 ligation induced by (a) cognate T helper-B cell interaction mediated by microbial superantigen (SAg); (b) contact-dependent interaction with CD40L+, but not CD40L- Jurkat mutant T cell clones; and (c) monoclonal anti-CD40, but not any of a panel of control antibodies. Enhanced B cell Fas/Apo-1 expression is functionally significant. Coculture of Ramos Burkitt's lymphoma line cells with irradiated SAg-reactive CD4+ T cells with SAg or CD40L+ Jurkat T cells results in B cell apoptosis, evidenced by reduced cell viability and DNA laddering. This process is augmented by the addition of anti-Apo-1/Fas monoclonal antibody, consistent with an acquired susceptibility to Apo-1/Fas-mediated apoptosis. These data support an immunoregulatory pathway in which seemingly contradictory signals involving the B cell proliferation/survival antigen CD40, as well as the Apo-1/Fas molecule, which mediates programmed cell death of lymphocytes, are linked in the process of human B cell activation.
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DOI：
10.1073/pnas.90.21.10340
发表时间：
1993-11-01
影响因子：
11.1
作者：
DRAPPA, J;BROT, N;ELKON, KB
通讯作者：
ELKON, KB
影响因子：
3.1
作者：
ATKIN, CL;WEI, SH;COLE, BC
通讯作者：
COLE, BC
DOI：
10.1073/pnas.91.11.4930
发表时间：
1994-05-24
影响因子：
11.1
作者：
HANABUCHI, S;KOYANAGI, M;OKUMURA, K
通讯作者：
OKUMURA, K
DOI：
10.1084/jem.175.4.1091
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Lederman S;Yellin MJ;Krichevsky A;Belko J;Lee JJ;Chess L
通讯作者：
Chess L
影响因子：
64.5
作者：
ARUFFO, A;FARRINGTON, M;OCHS, HD
通讯作者：
OCHS, HD