Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas.
Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas.
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DOI：
10.4049/jimmunol.0901689
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发表时间：
2010-07-01
期刊：
影响因子：
--
通讯作者：
Shimoda M
中科院分区：
文献类型：
--
作者：
Bolduc A;Long E;Stapler D;Cascalho M;Tsubata T;Koni PA;Shimoda M
CD 40/CD 40 L结合对于T细胞依赖性B细胞增殖和分化是必不可少的。然而，通过同源T-B相互作用的CD 40信号传导在生殖中心和记忆B细胞的产生中的确切作用仍不完全清楚。为了解决这一问题，将B细胞特异性CD 40 L转基因（CD 40 LBTg）引入具有B细胞限制性MHC II类缺陷的小鼠中。使用这个小鼠模型，我们表明，组成型CD 40 L表达的B细胞单独不能诱导生发中心分化的MHC II类缺陷的B细胞免疫后，T细胞依赖性抗原。因此，一些其他的MHC II类依赖性T细胞衍生的信号对于响应于T细胞依赖性Ag的生发中心B细胞的产生是必需的。事实上，CD 40 LBTg小鼠产生了复杂的Ag特异性IgG 1应答，与对照小鼠相比，早期的初级应答大大增强，但晚期的初级应答减少。我们还发现，在CD 40 LBTg小鼠中Ag特异性生发中心B细胞的频率在免疫后1周突然减少。结果，Ag特异性IgG 1长寿命浆细胞和记忆B细胞的数量减少。通过组织学，在CD 40 LBTg小鼠的Ag特异性生发中心附近的T细胞区域中发现了大量的Ag特异性浆细胞，暂时在初次应答的第二周。这些结果表明，B细胞上的CD 40 L表达过早地终止了它们正在进行的生殖中心反应并产生浆细胞。我们的研究结果支持了CD 40信号是生发中心反应的主动终止信号的观点。
CD40/CD40L engagement is essential to T cell-dependent B cell proliferation and differentiation. However, the precise role of CD40 signaling through cognate T–B interaction in the generation of germinal center and memory B cells is still incompletely understood. To address this issue, a B cell-specific CD40L transgene (CD40LBTg) was introduced into mice with B cell-restricted MHC class II deficiency. Using this mouse model, we show that constitutive CD40L expression on B cells alone could not induce germinal center differentiation of MHC class II-deficient B cells after immunization with T cell-dependent Ag. Thus, some other MHC class II-dependent T cell-derived signals are essential for the generation of germinal center B cells in response to T cell-dependent Ag. In fact, CD40LBTg mice generated a complex Ag-specific IgG1 response, which was greatly enhanced in early, but reduced in late, primary response compared with control mice. We also found that the frequency of Ag-specific germinal center B cells in CD40LBTg mice was abruptly reduced 1 wk after immunization. As a result, the numbers of Ag-specific IgG1 long-lived plasma cells and memory B cells were reduced. By histology, large numbers of Ag-specific plasma cells were found in T cell areas adjacent to Ag-specific germinal centers of CD40LBTg mice, temporarily during the second week of primary response. These results indicate that CD40L expression on B cells prematurely terminated their ongoing germinal center response and produced plasma cells. Our results support the notion that CD40 signaling is an active termination signal for germinal center reaction.
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影响因子：
4.4
作者：
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通讯作者：
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作者：
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作者：
Filion, LG;Matusevicius, D;Freedman, MS
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DOI：
10.1084/jem.186.3.439
发表时间：
1997-08-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Fukuda T;Yoshida T;Okada S;Hatano M;Miki T;Ishibashi K;Okabe S;Koseki H;Hirosawa S;Taniguchi M;Miyasaka N;Tokuhisa T
通讯作者：
Tokuhisa T