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标题: PD-1阻断部分恢复慢性乙型肝炎感染中功能失调的病毒特异性B [打印本页]

作者: StephenW 时间: 2018-9-18 16:29 标题: PD-1阻断部分恢复慢性乙型肝炎感染中功能失调的病毒特异性B

PD-1 blockade partially recovers dysfunctional virus–specific B cells in chronic hepatitis B infection
Loghman Salimzadeh,1,2,3 Nina Le Bert,1 Charles-A. Dutertre,1,2 Upkar S. Gill,4 Evan W. Newell,2 Christian Frey,5 Magdeleine Hung,5 Nikolai Novikov,5 Simon Fletcher,5 Patrick T.F. Kennedy,4 and Antonio Bertoletti1,2

First published August 7, 2018 - More info
Related 1 article:
Entering the spotlight: hepatitis B surface antigen–specific B cells
Christoph Neumann-Haefelin, Robert Thimme
Category: Commentary

Abstract

Chronic HBV (CHB) infection suppresses virus-specific T cells, but its impact on humoral immunity has been poorly analyzed. Here, we developed a dual-staining method that utilizes hepatitis B virus (HBV) surface antigens (HBsAg) labeled with fluorochromes as “baits” for specific ex vivo detection of HBsAg-specific B cells and analysis of their quantity, function, and phenotype. We studied healthy vaccinated subjects (n = 18) and patients with resolved (n = 21), acute (n = 11), or chronic (n = 96) HBV infection and observed that frequencies of circulating HBsAg-specific B cells were independent of HBV infection status. In contrast, the presence of serum HBsAg affected function and phenotype of HBsAg-specific B cells that were unable to mature in vitro into Ab-secreting cells and displayed an increased expression of markers linked to hyperactivation (CD21lo) and exhaustion (PD-1). Importantly, B cell alterations were not limited to HBsAg-specific B cells, but affected the global B cell population. HBsAg-specific B cell maturation could be partially restored by a method involving the combination of the cytokines IL-2 and IL-21 and CD40L-expressing feeder cells and was further boosted by the addition of anti–PD-1 Abs. In conclusion, HBV infection has a marked impact on global and HBV-specific humoral immunity, yet HBsAg-specific B cells are amenable to a partial rescue by B cell–maturing cytokines and PD-1 blockade.

作者: StephenW 时间: 2018-9-18 16:30

PD-1阻断部分恢复慢性乙型肝炎感染中功能失调的病毒特异性B细胞
Loghman Salimzadeh，1,2,3 Nina Le Bert，1 Charles-A。 Dutertre，1,2 Upkar S. Gill，4 Evan W. Newell，2 Christian Frey，5 Magdeleine Hung，5 Nikolai Novikov，5 Simon Fletcher，5 Patrick T.F. Kennedy，4和Antonio Bertoletti1,2

首次发布于2018年8月7日 - 更多信息
相关1篇文章：
进入聚光灯：乙型肝炎表面抗原特异性B细胞
Christoph Neumann-Haefelin，Robert Thimme
类别：评论

抽象

慢性HBV（CHB）感染抑制病毒特异性T细胞，但其对体液免疫的影响很少被分析。在这里，我们开发了一种双染色方法，利用荧光染料标记的乙型肝炎病毒（HBV）表面抗原（HBsAg）作为特异性体外检测HBsAg特异性B细胞的“诱饵”，并分析其数量，功能和表型。。我们研究了健康接种受试者（n = 18）和已解决（n = 21），急性（n = 11）或慢性（n = 96）HBV感染的患者，并观察到循环HBsAg特异性B细胞的频率独立于HBV感染状况。相反，血清HBsAg的存在影响HBsAg特异性B细胞的功能和表型，这些细胞在体外不能成熟为分泌Ab的细胞，并且表现出与过度活化（CD21lo）和衰竭（PD-1）相关的标志物表达的增加。。重要的是，B细胞改变不仅限于HBsAg特异性B细胞，而且影响全球B细胞群。 HBsAg特异性B细胞成熟可以通过涉及细胞因子IL-2和IL-21与表达CD40L的饲养细胞的组合的方法部分恢复，并通过添加抗PD-1抗体进一步加强。总之，HBV感染对全球和HBV特异性体液免疫具有显着影响，但HBsAg特异性B细胞可通过B细胞成熟细胞因子和PD-1阻断进行部分拯救。

作者: StephenW 时间: 2018-9-18 16:30

https://www.jci.org/articles/view/121957

作者: 齐欢畅 时间: 2018-9-18 18:48

StephenW 发表于 2018-9-18 16:30
https://www.jci.org/articles/view/121957

英文看着累，大佬解读一下吧！~~

作者: StephenW 时间: 2018-9-18 21:11

回复齐欢畅的帖子

Antonio Bertoletti是你最喜欢的新加坡研究员(Lion TCR-T).

作者: 齐欢畅 时间: 2018-9-18 21:16

StephenW 发表于 2018-9-18 21:11
回复齐欢畅的帖子

Antonio Bertoletti是你最喜欢的新加坡研究员(Lion TCR-T).

看来有料。

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