Differential regulation of marginal zone and follicular B cell responses by CD83.

Differential regulation of marginal zone and follicular B cell responses by CD83.
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CD83 对边缘区和滤泡 B 细胞反应的差异调节

DOI:
10.1093/intimm/dxt021
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发表时间:
2013
影响因子:
4.4
通讯作者:
Osterloh A
Osterloh A
中科院分区:
医学3区
文献类型:
--
作者:
Uhde M;Kuehl S;Fleischer B;Osterloh A

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CD83在B细胞上的转基因过表达导致对BCR参与的反应降低,但在LPS刺激下IL-10的分泌增强。在本研究中,我们分析了CD83对BCR或TLR4刺激不同B细胞亚群的差异影响。野生型和CD83转基因(CD83tg) B细胞对BCR刺激均不产生任何IL-10。BCR参与导致LYN、SYK和ERK1/2的激活减少,导致所有CD83tg B细胞亚群中增殖细胞数量减少。此外,CD83tg在卵泡(FO)而非边缘区(MZ)或过渡性(TN) B细胞中表现出明显的细胞死亡。相比之下,LPS刺激导致CD83tg FO, MZ和TN B细胞的增殖频率正常,尽管TLR4的参与并没有使FO B细胞免于凋亡。此外,LPS刺激导致CD83tg MZ B细胞产生高IL-10,这些细胞对LPS刺激的反应是增强ERK1/2激活。最后,我们发现CD83与BCR复合物以及LPS受体复合物共定位,表明CD83与这两种信号复合物的组分相互作用。综上所述,本研究结果表明CD83已经抑制了BCR信号的启动,导致所有B细胞的激活信号不足,并降低了存活,尤其是FO B细胞。另一方面,CD83支持tlr4介导的IL-10仅在MZ B细胞中释放。因此,CD83不同地调节FO和MZ B细胞的反应。
Transgenic over-expression of CD83 on B cells leads to a reduced response to BCR engagement but to an enhanced secretion of IL-10 upon LPS stimulation. In this study, we analyzed the differential influence of CD83 on the stimulation of different B cell subsetsviathe BCR or TLR4. Neither wild type nor CD83 transgenic (CD83tg) B cells produced any IL-10 in response to BCR stimulation. BCR engagement led to reduced activation of LYN, SYK and ERK1/2 resulting in reduced numbers of proliferating cells in all CD83tg B cell subsets. Moreover, CD83tg follicular (FO) but not marginal zone (MZ) or transitional (TN) B cells showed significantly enhanced cell death. In contrast, LPS stimulation led to normal frequencies of proliferating CD83tg FO, MZ and TN B cells although TLR4 engagement did not rescue FO B cells from apoptosis. Furthermore, LPS stimulation led to high IL-10 production derived from CD83tg MZ B cells that reacted to LPS stimulation with enhanced ERK1/2 activation. Finally, we show that CD83 co-localizes with the BCR complex as well as with the LPS receptor complex suggesting that CD83 interacts with components of both signaling complexes. Taken together, the results of this study show that CD83 already inhibits the initiation of BCR signaling leading to insufficient activation signals in all B cells and reduced survival especially of FO B cells. On the other hand, CD83 supports TLR4-mediated IL-10 release exclusively in MZ B cells. Thus, CD83 differentially modulates FO and MZ B cell responses.
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发表时间: 2001-05-01
期刊: IMMUNITY
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发表时间: 2003
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影响因子: 11.4
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