循环和肝内抗病毒B细胞在乙型肝炎中有缺陷。

StephenW

J Clin Invest. 2018 Aug 9. pii: 121960. doi: 10.1172/JCI121960. [Epub ahead of print]
Circulating and intrahepatic antiviral B cells are defective in hepatitis B.
Burton AR, Pallett LJ, McCoy LE, Suveizdyte K, Amin OE, Swadling L, Alberts E, Davidson BR, Kennedy PT, Gill US, Mauri C, Blair PA, Pelletier N, Maini MK.
Abstract

B cells are increasingly recognised to play an important role in the ongoing control of hepatitis B virus (HBV). The development of antibodies against the viral surface antigen (HBsAg) constitutes the hallmark of resolution of acute infection and is a therapeutic goal for functional cure of chronic HBV (CHB). We characterised 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 signalling, homing, differentiation into antibody-producing cells, survival and antiviral/pro-inflammatory 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.
KEYWORDS:

B cells; Hepatitis; Immunology; Infectious disease; Tolerance

PMID:
    30091725
DOI:
    10.1172/JCI121960

StephenW

J Clin Invest。 2018年8月9日.pii：121960。doi：10.1172 / JCI121960。 [提前打印]
循环和肝内抗病毒B细胞在乙型肝炎中有缺陷。
Burton AR，Pallett LJ，McCoy LE，Suveizdyte K，Amin OE，Swadling L，Alberts E，Davidson BR，Kennedy PT，Gill US，Mauri C，Blair PA，Pelletier N，Maini MK。
抽象

人们越来越认识到B细胞在持续控制乙型肝炎病毒（HBV）中发挥重要作用。抗病毒表面抗原（HBsAg）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，其中包括PD-1的抑制性受体的高表达。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，这可以通过PD-1阻断部分地挽救。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。
关键词：

B细胞;肝炎;免疫学;传染病;公差

结论：
    30091725
DOI：
    10.1172 / JCI121960