Tumor-derived autophagosomes (DRibbles) induce B cell activation in a TLR2-MyD88 dependent manner.
Tumor-derived autophagosomes (DRibbles) induce B cell activation in a TLR2-MyD88 dependent manner.
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肿瘤源性自噬体 (DRibbles) 以 TLR2-MyD88 依赖性方式诱导 B 细胞激活
DOI：
10.1371/journal.pone.0053564
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang LX
中科院分区：
文献类型：
--
作者：
Li W;Zhou M;Ren H;Hu HM;Lu L;Cao M;Wang LX
以前，我们已经证明，从肿瘤细胞中分离的自噬体可以有效地交叉致敏肿瘤反应性幼稚T细胞，并在临床前小鼠模型中介导肿瘤消退。然而，肿瘤来源的自噬体，在这里我们指的是DRibbles，对B细胞的影响迄今尚未研究。目前，我们发现从小鼠肝癌细胞系Hep 1 -6中产生的DRibbles静脉注射到小鼠体内后，诱导B细胞活化。B细胞群显著扩增，并成功诱导Hep 1 -6肿瘤特异性抗体的产生。此外，体外研究表明，DRibbles可以诱导比全肿瘤细胞裂解物更有效的B细胞增殖和活化，抗体产生和细胞因子分泌。值得注意的是，我们发现B细胞激活需要蛋白质，而不是DRibbles中的DNA。我们进一步表明，B细胞可以捕获DRibbles并在DRibbles中呈递抗原以直接诱导T细胞活化。此外，我们发现B细胞活化、抗体产生、细胞因子分泌和抗原交叉呈递是TLR 2-MyD 88通路依赖的。这些研究表明，肿瘤源性自噬体（DRibbles）主要依赖其蛋白组分，通过TLR 2/MyD 88依赖的方式有效地诱导B细胞活化、抗体产生、细胞因子分泌和抗原交叉呈递。
Previously, we have documented that isolated autophagosomes from tumor cells could efficiently cross-prime tumor-reactive naïve T cells and mediate tumor regression in preclinical mouse models. However, the effect of tumor-derived autophagosomes, here we refer as to DRibbles, on B cells has not been studied so far. At present study, we found that DRibbles generated from a murine hepatoma cell line Hep1-6, induced B-cell activation after intravenous injection into mice. B-cell populations were significantly expanded and the production of Hep1-6 tumor-specific antibodies was successfully induced. Moreover, in vitro studies showed that DRibbles could induce more efficient B-cell proliferation and activation, antibody production, and cytokine secretion than whole tumor cell lysates. Notably, we found that B-cell activation required proteins but not DNA in the DRibbles. We further showed that B cells could capture DRibbles and present antigens in the DRibbles to directly induce T cell activation. Furthermore, we found that B-cell activation, antibody production, cytokine secretion and antigen cross-presentation were TLR2-MyD88 pathway dependent. Taken together, the present studies demonstrated that tumor-derived autophagosomes (DRibbles) efficiently induced B cells activation, antibody production, cytokine secretion and antigen cross-presentation mainly depending on their protein component via TLR2/MyD88 dependent manner.
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DOI：
10.1083/jcb.151.5.1025
发表时间：
2000-11-27
期刊：
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