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

StephenW

J Clin Invest. 2018 Aug 7. pii: 121957. doi: 10.1172/JCI121957. [Epub ahead of print]
PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection.
Salimzadeh L, Le Bert N, Dutertre CA, Gill US, Newell EW, Frey C, Hung M, Novikov N, Fletcher S, Kennedy PT, Bertoletti A.
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, which utilizes HBsAg labelled 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 are independent of the HBV infection status. In contrast, serum HBsAg presence affects function and phenotype of HBsAg-specific B cells that were unable to mature in vitro into antibody-secreting cells and displayed an increased expression of markers linked to hyperactivation (CD21low) 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 IL-2, IL-21 and CD40L-expressing feeder cells, and further boosted by addition of anti-PD-1 antibodies.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.
KEYWORDS:

B cells; Hepatitis; Hepatology; Infectious disease

PMID:
    30084841
DOI:
    10.1172/JCI121957

StephenW

J Clin Invest。 2018年8月7日.pii：121957。doi：10.1172 / JCI121957。 [提前打印]
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。
Salimzadeh L，Le Bert N，Dutertre CA，Gill US，Newell EW，Frey C，Hung M，Novikov N，Fletcher S，Kennedy PT，Bertoletti A.
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，我们开发了一种双重染色方法，利用荧光染料标记的HBsAg作为“诱饵”，用于特异性离体检测HBsAg特异性B细胞并分析其数量，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，所述HBsAg特异性B细胞不能在体外成熟为抗体分泌细胞，并且表现出与过度活化（CD21low）和衰竭（PD-1）相关的标志物的表达增加。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IL-2，IL-21和CD40L表达饲养细胞的组合的方法部分恢复，并且通过添加抗PD-1抗体进一步加强。结论，HBV感染具有对全球和HBV特异性体液免疫有显着影响，但HBsAg特异性B细胞适合B细胞成熟细胞因子和PD-1阻断的部分拯救。
关键词：

B细胞;肝炎;肝病;传染病

结论：
    30084841
DOI：
    10.1172 / JCI121957

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