HBV在B细胞上诱导抑制性FcRL受体并且使B细胞-T滤泡辅助细胞轴

StephenW

HBV induces inhibitory FcRL receptor on B cells and dysregulates B cell-T follicular helper cell axis

    Bhawna Poonia, Natarajan Ayithan, Madhuparna Nandi, Henry Masur & Shyam Kottilil

Scientific Reportsvolume 8, Article number: 15296 (2018) | Download Citation
Abstract

Spontaneous or treatment induced seroconversion in chronic HBV infection is rare and generation of anti-HBs antibodies is the current goal of HBV therapeutics. Here we investigated B and follicular T helper (Tfh) cell defects that persist in HBV infection despite long-term nucleos(t)ide analog (NUC) treatment and possible mechanisms behind them. RNA sequencing revealed that patient B cells have upregulated expression of multiple inhibitory receptors including members of FcRL family and downregulation of genes involved in antigen presentation. An expansion of atypical memory CD19+CD10−CD27−CD21− subset of B cells, that express high levels of FcRL5, is persistently present in patients. HBs antigen specific IgG response is concentrated in classical memory and not in atypical memory subset, confirming dysfunction of this subset. Activated Tfh, which expressed excessive CD40L upon polyclonal stimulation, were present in patients. Incubation of B cells from healthy individuals with HBV core (HBc) or CD40L resulted in induction of inhibitory receptors FcRL4, FcRL5 and PD-1 on CD19+ cells and resulted in altered B cell phenotypes. Mechanistically, HBc binds B cells and causes proliferation specifically of FcRL5+ B cell subset. Our results provide evidence that HBV directly causes upregulation of inhibitory pathways in B cells resulting in an accumulation of atypical B cells that lack anti-HBs function.

StephenW

HBV在B细胞上诱导抑制性FcRL受体并且使B细胞-T滤泡辅助细胞轴失调

    Bhawna Poonia，Natarajan Ayithan，Madhuparna Nandi，Henry Masur和Shyam Kottilil

Scientific Reportsvolume 8，货号：15296（2018）|下载引文
抽象

慢性HBV感染中的自发或治疗诱导的血清转化是罕见的，并且抗HBs抗体的产生是HBV治疗的当前目标。在这里，我们研究了B和卵泡T辅助（Tfh）细胞缺陷，这些缺陷在HBV感染中持续存在，尽管长期核苷酸（t）ide类似物（NUC）治疗及其背后的可能机制。 RNA测序显示，患者B细胞具有上调多种抑制性受体的表达，包括FcRL家族成员和参与抗原呈递的基因的下调。表达高水平FcRL5的非典型记忆CD19 + CD10-CD27-CD21-亚型B细胞的扩增持续存在于患者体内。 HBs抗原特异性IgG应答集中在经典记忆中而非非典型记忆子集中，证实了该亚组的功能障碍。在患者中存在活化的Tfh，其在多克隆刺激时表达过量的CD40L。来自具有HBV核心（HBc）或CD40L的健康个体的B细胞的孵育导致CD19 +细胞上的抑制性受体FcRL4，FcRL5和PD-1的诱导，并导致B细胞表型的改变。机械地，HBc结合B细胞并特异性地引起FcRL5 + B细胞亚群的增殖。我们的结果提供证据表明HBV直接导致B细胞中抑制性途径的上调，导致缺乏抗HBs功能的非典型B细胞的积累。

StephenW

https://www.nature.com/articles/ ... B7BAF2A6AD1888D64ED