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Extracellular Release of Antigen by Dendritic Cell Regurgitation Promotes B Cell Activation through NF-κB/cRel
The Journal of Immunology ( IF 4.4 ) Pub Date : 2020-06-24 , DOI: 10.4049/jimmunol.1900394
Houssam El-Barbry 1 , Marisa Capitao 1 , Sarah Barrin 1 , Samir Amziani 1 , Pascal Pierre Paul 1 , Susanna Borreill 1 , Thomas Guilbert 1 , Emmanuel Donnadieu 1 , Florence Niedergang 1 , Fatah Ouaaz 2
Affiliation  

Key Points Dendritic cells transfer Ags to and activate B cells in vivo. Ags released from dendritic cells by regurgitation promote B cell activation. Early B cell activation by dendritic cell regurgitation requires NF-κB/cRel. Visual Abstract Dendritic cells (DCs) are professional APCs, which sample Ags in the periphery and migrate to the lymph node where they activate T cells. DCs can also present native Ag to B cells through interactions observed both in vitro and in vivo. However, the mechanisms of Ag transfer and B cell activation by DCs remain incompletely understood. In this study, we report that murine DCs are an important cell transporter of Ag from the periphery to the lymph node B cell zone and also potent inducers of B cell activation both in vivo and in vitro. Importantly, we highlight a novel extracellular mechanism of B cell activation by DCs. In this study, we demonstrate that Ag released upon DC regurgitation is sufficient to efficiently induce early B cell activation, which is BCR driven and mechanistically dependent on the nuclear accumulation of the transcription factor NF-κB/cRel. Thus, our study provides new mechanistic insights into Ag delivery and B cell activation modalities by DCs and a promising approach for targeting NF-κB/cRel pathway to modulate the DC-elicited B cell responses.

中文翻译:

树突状细胞反流引起的细胞外抗原释放通过 NF-κB/cRel 促进 B 细胞活化

关键点 树突状细胞在体内将 Ags 转移到 B 细胞并激活 B 细胞。通过反流从树突细胞释放的抗原促进 B 细胞活化。树突状细胞反流引起的早期 B 细胞激活需要 NF-κB/cRel。Visual Abstract 树突状细胞 (DC) 是专业的 APC,它在外周采集 Ags 并迁移到淋巴结,在那里激活 T 细胞。DC 还可以通过在体外和体内观察到的相互作用将天然 Ag 呈递给 B 细胞。然而,DCs 的 Ag 转移和 B 细胞激活机制仍未完全了解。在这项研究中,我们报告说,鼠 DCs 是 Ag 从外围到淋巴结 B 细胞区的重要细胞转运蛋白,也是体内和体外 B 细胞活化的有效诱导剂。重要的,我们强调了 DC 激活 B 细胞的一种新的细胞外机制。在这项研究中,我们证明 DC 反流时释放的 Ag 足以有效诱导早期 B 细胞激活,这是 BCR 驱动的,并且在机制上依赖于转录因子 NF-κB/cRel 的核积累。因此,我们的研究为 DC 的 Ag 递送和 B 细胞激活方式提供了新的机制见解,并为靶向 NF-κB/cRel 通路以调节 DC 引发的 B 细胞反应提供了一种有前景的方法。
更新日期:2020-06-24
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