循环和肝内抗病毒B细胞在乙型肝炎中有缺陷

StephenW

Circulating and intrahepatic antiviral B cells are defective in hepatitis B        [url=]Alice R. Burton,1[/url]        [url=]Laura J. Pallett,1[/url]        [url=]Laura E. McCoy,1[/url]        [url=]Kornelija Suveizdyte,1[/url]        [url=]Oliver E. Amin,1[/url]        [url=]Leo Swadling,1[/url]        [url=]Elena Alberts,1[/url]        [url=]Brian R. Davidson,2[/url]        [url=]Patrick T.F. Kennedy,3[/url]        [url=]Upkar S. Gill,3[/url]        [url=]Claudia Mauri,4[/url]        [url=]Paul A. Blair,4[/url]        [url=]Nadege Pelletier,5 and[/url]        [url=]Mala K. Maini1[/url]                                                                                                               

First published August 9, 2018-[url=]More info[/url]

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Related article:Entering the spotlight: hepatitis B surface antigen–specific B cells

Christoph Neumann-Haefelin, Robert Thimme


Category:Commentary

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                        AbstractB cells are increasingly recognized as playing an important role in the ongoing control of hepatitis B virus (HBV). The development of antibodies against the viral surface antigen (HBV surface antigen [HBsAgs]) constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic HBV (CHB). We characterized B cells directly ex vivo from the blood and liver of patients with CHB to investigate constraints on their antiviral potential. Unexpectedly, we found that HBsAg-specific B cells persisted in the blood and liver of many patients with CHB and were enriched for T-bet, a signature of antiviral potential in B cells. However, purified, differentiated HBsAg-specific B cells from patients with CHB had defective antibody production, consistent with undetectable anti-HBs antibodies in vivo. HBsAg-specific and global B cells had an accumulation of CD21–CD27– atypical memory B cells (atMBC) with high expression of inhibitory receptors, including PD-1. These atMBC demonstrated altered signaling, homing, differentiation into antibody-producing cells, survival, and antiviral/proinflammatory cytokine production that could be partially rescued by PD-1 blockade. Analysis of B cells within healthy and HBV-infected livers implicated the combination of this tolerogenic niche and HBV infection in driving PD-1hiatMBC and impairing B cell immunity.

Graphical Abstract

StephenW

循环和肝内抗病毒B细胞在乙型肝炎中有缺陷
Alice R. Burton，1 Laura J. Pallett，1 Laura E. McCoy，1 Kornelija Suveizdyte，1 Oliver E. Amin，1 Leo Swadling，1 Elena Alberts，1 Brian R. Davidson，2 Patrick T.F. Kennedy，3 Upkar S. Gill，3 Claudia Mauri，4 Paul A. Blair，4 Nadege Pelletier，5和Mala K. Maini1

首次发布于2018年8月9日 - 更多信息
相关文章：
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

    B细胞越来越被认为在持续控制乙型肝炎病毒（HBV）中发挥着重要作用。针对病毒表面抗原（HBV表面抗原[HBsAgs]）的抗体的开发构成了解决急性感染的标志，并且是慢性HBV（CHB）功能性治愈的治疗目标。我们直接从CHB患者的血液和肝脏中体外鉴定B细胞，以研究其抗病毒潜力的限制。出乎意料的是，我们发现HBsAg特异性B细胞持续存在于许多CHB患者的血液和肝脏中，并且富集了T-bet，这是B细胞中抗病毒潜力的标志。然而，来自CHB患者的纯化的，分化的HBsAg特异性B细胞具有缺陷抗体产生，与体内不可检测的抗HBs抗体一致。 HBsAg特异性和全局B细胞具有CD21-CD27-非典型记忆B细胞（atMBC）的积累，具有高表达的抑制性受体，包括PD-1。这些atMBC表现出改变的信号传导，归巢，分化成抗体产生细胞，存活和抗病毒/促炎细胞因子的产生，其可以通过PD-1阻断部分地拯救。对健康和HBV感染的肝脏中的B细胞的分析暗示这种致耐受性生态位和HBV感染的组合在驱动PD-1hiatMBC和损害B细胞免疫中。

StephenW

https://www.jci.org/articles/vie ... %2C+issue+published