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肿瘤衍生自噬体(DRibbles)激活人 B 细胞诱导有效的抗原特异性人记忆 T 细胞应答。

Tumor-Derived Autophagosomes (DRibbles) Activate Human B Cells to Induce Efficient Antigen-Specific Human Memory T-Cell Responses.

机构信息

Department of Pathology and Pathophysiology, School of Medicine & Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Department of Microbiology and Immunology, Medical School, Southeast University, Nanjing, China.

出版信息

Front Immunol. 2021 May 26;12:675822. doi: 10.3389/fimmu.2021.675822. eCollection 2021.

Abstract

We have reported that tumor-derived autophagosomes (DRibbles) were efficient carriers of tumor antigens and DRibbles antigens could be present by DRibbles-activated B cells to stimulate effect and naïve T cells in mice. However, the effect of DRibbles on human B cells remains unclear. Herein, we found that DRibbles can also efficiently induce proliferation and activation of human B cells and lead to the production of chemokines, cytokines and hematopoietic growth factors. We further demonstrated human B cells can effectively phagocytose DRibbles directly and cross-present DRibbles antigens to stimulate antigen-specific memory T cells. Furthermore, we found that membrane-bound high-mobility group B1 (HMGB1) on DRibbles was crucial for inducing human B cells activation. Therefore, these findings provide further evidence to promote the clinical application of B-DRibbles vaccines.

摘要

我们曾报道过,肿瘤来源的自噬体(DRibbles)是肿瘤抗原的有效载体,DRibbles 抗原可通过 DRibbles 激活的 B 细胞呈递,从而刺激小鼠中的效应和初始 T 细胞。然而,DRibbles 对人 B 细胞的影响尚不清楚。在此,我们发现 DRibbles 还可以有效地诱导人 B 细胞的增殖和活化,并导致趋化因子、细胞因子和造血生长因子的产生。我们进一步证明,人 B 细胞可以有效地直接吞噬 DRibbles,并交叉呈递 DRibbles 抗原,以刺激抗原特异性记忆 T 细胞。此外,我们发现 DRibbles 上的膜结合高迁移率族蛋白 B1(HMGB1)对于诱导人 B 细胞的活化至关重要。因此,这些发现为促进 B-DRibbles 疫苗的临床应用提供了进一步的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e447/8187759/e127e701687a/fimmu-12-675822-g001.jpg

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