CD83 Modulates B Cell Function In Vitro: Increased IL-10 and Reduced Ig Secretion by CD83Tg B Cells
CD83 Modulates B Cell Function In Vitro: Increased IL-10 and Reduced Ig Secretion by CD83Tg B Cells
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DOI：
10.1371/journal.pone.0000755
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发表时间：
2007-01-01
期刊：
影响因子：
3.7
通讯作者：
Breloer, Minka
中科院分区：
文献类型：
--
作者：
Kretschmer, Birte;Luethje, Katja;Breloer, Minka
小鼠跨膜糖蛋白CD 83是胸腺T细胞成熟和外周T细胞应答的重要调节因子。最近，我们报道了CD 83在B细胞上也具有功能：CD 83的普遍转基因（Tg）表达干扰免疫球蛋白（IG）对感染性病原体和对T细胞依赖性以及T细胞非依赖性模型抗原免疫的应答。在这里，我们比较了过表达CD 83的CD 83 Tg B细胞和显示出显著降低的CD 83表达的CD 83突变体（CD 83 mu）B细胞的功能。与CD 83表达相关，在CD 83 Tg B细胞中，活化标志物CD 86和MHC-II的基础表达以及脂多糖（LPS）诱导的表达显著增加，而在CD 83 mu B细胞中，活化标志物CD 86和MHC-II的基础表达以及脂多糖诱导的表达显著降低。野生型B细胞在BCR或TLR接合后3小时内通过从头蛋白质合成快速上调CD 83。CD 83在CD 83 Tg B细胞上的被迫过早过表达导致钙信号传导减少、IG分泌减少和体外活化后IL-10产生的急剧增加。这种改变的表型是由B细胞自身上表达的CD 83介导的，因为它是在没有辅助细胞的情况下观察到的。与该发现一致，纯化的CD 83 μ B细胞在体外LPS刺激后显示出降低的IL-10产生和略微增加的IG分泌。综上所述，我们的数据有力地表明，CD 83是由B细胞活化后表达，并有助于调节B细胞的功能。
The murine transmembrane glycoprotein CD83 is an important regulator for both thymic T cell maturation and peripheral T cell responses. Recently, we reported that CD83 also has a function on B cells: Ubiquitous transgenic (Tg) expression of CD83 interfered with the immunoglobulin (Ig) response to infectious agents and to T cell dependent as well as T cell independent model antigen immunization. Here we compare the function of CD83Tg B cells that overexpress CD83 and CD83 mutant (CD83mu) B cells that display a drastically reduced CD83 expression. Correlating with CD83 expression, the basic as well as the lipopolysaccharide (LPS) induced expression of the activation markers CD86 and MHC-II are significantly increased in CD83Tg B cells and reciprocally decreased in CD83mu B cells. Wild-type B cells rapidly upregulate CD83 within three hours post BCR or TLR engagement by de novo protein synthesis. The forced premature overexpression of CD83 on the CD83Tg B cells results in reduced calcium signaling, reduced Ig secretion and a reciprocally increased IL-10 production upon in vitro activation. This altered phenotype is mediated by CD83 expressed on the B cells themselves, since it is observed in the absence of accessory cells. In line with this finding, purified CD83mu B cells displayed a reduced IL-10 production and slightly increased Ig secretion upon LPS stimulation in vitro. Taken together, our data strongly suggest that CD83 is expressed by B cells upon activation and contributes to the regulation of B cell function.