Fas ligation induces apoptosis of CD40-activated human B lymphocytes.
Fas ligation induces apoptosis of CD40-activated human B lymphocytes.
复制标题
FAS结扎诱导CD40激活的人B淋巴细胞的凋亡。
DOI：
10.1084/jem.182.5.1265
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发表时间：
1995-11-01
影响因子：
15.3
通讯作者：
Banchereau, Jacques
中科院分区：
文献类型：
--
作者：
Garrone, Pierre;Neidhart, Eve-Marie;Garcia, Eric;Galibert, Laurent;Van Kooten, Cees;Banchereau, Jacques
由于CD 40/CD 40配体（CD 40 Lig）相互作用在体内对于表达Fas（Apo- 1/CD 95）的生殖中心B细胞的产生是必不可少的，我们探讨了CD 40参与是否可以调节人B淋巴细胞上Fas的表达和功能。通过密度梯度离心分离的静息扁桃体B细胞表达不存在或低水平的Fas。然而，使用重组人CD 40 Lig或交联抗CD 40 mAb，它们可以在连接其CD 40后被诱导迅速表达Fas。相反，固定化的抗κ和λ抗体与B细胞抗原受体的结合并不启动Fas表达。加入抗Fas mAb CH 11可抑制CD 40诱导的B细胞生长的后期，这是细胞凋亡的结果。此外，Fas连接抑制CD 40活化的B细胞对重组细胞因子如白细胞介素（IL）-2，IL-4和IL-10的增殖和IG分泌，以及植物血凝素活化的T细胞的富含精氨酸的上清液，表明这些B细胞嗜性因子都不能阻止Fas诱导的死亡。综上所述，本研究结果表明，B细胞上的CD 40抗原的参与诱导Fas表达并使它们对Fas介导的凋亡敏感。在CD 40活化后对Fas连接的延迟的功能应答可能代表限制在T-B细胞相互作用期间产生的特定B细胞克隆的大小的方式。
Since CD40/CD40 ligand (CD40Lig) interactions are essential in vivo for the generation of germinal center B cells that express Fas (Apo- 1/CD95), we explored whether CD40 engagement may modulate Fas expression and function on human B lymphocytes. Resting tonsil B cells, isolated by density gradient centrifugation, express either absent or low levels of Fas. They could be induced to promptly express Fas after ligation of their CD40, however, using either a recombinant human CD40Lig or a cross-linked anti-CD40 mAb. In contrast, engagement of the B cell antigen receptor by immobilized anti-kappa and -lambda antibodies did not turn on Fas expression. Addition of anti-Fas mAb CH11 inhibited the later phases of CD40-induced B cell growth as a result of apoptotic cell death. Furthermore, Fas ligation inhibited proliferation and Ig secretion of CD40-activated B cells in response to recombinant cytokines such as interleukin (IL)-2, IL-4, and IL-10, as well as a cytokine-rich supernatant of phytohemagglutinin-activated T cells, indicating that none of those B cell tropic factors were able to prevent the Fas-induced death. Taken together, the present results show that engagement of CD40 antigen on B cells induces Fas expression and sensitizes them to Fas-mediated apoptosis. The delayed functional response to Fas ligation after CD40 activation may represent a way to limit the size of a specific B cell clone that is generated during T-B cell interactions.
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DOI：
10.1084/jem.173.3.747
发表时间：
1991-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gascan H;Gauchat JF;Roncarolo MG;Yssel H;Spits H;de Vries JE
通讯作者：
de Vries JE
影响因子：
56.9
作者：
ARPIN, C;DECHANET, J;LIU, YJ
通讯作者：
LIU, YJ
影响因子：
15.3
作者：
Foy, Teresa M.;Laman, Jon D.;Ledbetter, Jeffrey A.;Aruffo, Alejandro;Claassen, Eric;Noelle, Randolph J.
通讯作者：
Noelle, Randolph J.
影响因子：
64.8
作者：
BANCHEREAU, J;ROUSSET, F
通讯作者：
ROUSSET, F
影响因子：
4.4
作者：
COCKS, BG;MALEFYT, RD;AVERSA, G
通讯作者：
AVERSA, G