EASL 2018 SAT-413 功能失调的表面抗原特异性记忆B细胞 在慢性乙

StephenW

EASL 2018 SAT-413
Dysfunctional surface antigen-specific memory B cells
accumulate in chronic hepatitis B infection
A. Burton1, L.J. Pallett2, L. Mccoy1, K. Suveizdyte1, O.E. Amin1, F. Froghi3,
B.R. Davidson3, U.S. Gill4, P.A. Blair5, C. Mauri5, N. Pelletier6,M. Maini1.
1UCL, Division of Infection and Immunity, London, United Kingdom;
2Division of Infection & Immunity, London, United Kingdom; 3UCL,
Institute of Liver and Digestive Health, London, United Kingdom; 4Barts
and the London, Centre for Immunobiology, London, United Kingdom;
5UCL, Division of Medicine, London, United Kingdom; 6Roche Innovation
Center, Roche Pharma and Early Research Development, Basel,
Switzerland
Email: [email protected]
Background and Aims: One important and under-researched
component of the natural control of hepatitis B (HBV) infection is
the development of antibodies against HBV surface antigen (HBsAg;
anti-HBs), which are a hallmark of functional cure. The production of
insufficient antibodies to neutralise the large quantities of circulating
HBsAg suggests there may be defects in the global and/or HBsAgspecific
memory B cell compartments.
Method: Using a novel bait reagent and 16-color flow cytometry, we
have comprehensively analysed the phenotype and function of global
and HBsAg-specific B cell subsets in a heterogeneous cohort of
patients with chronic HBV infection (CHB) and HBV-vaccinated
healthy controls.
Results: We show that HBsAg-specific B cells are detectable in CHB,
despite the lack of circulating anti-HBs antibodies in these patients.
However, in patients with CHB, HBsAg-specific memory B cells with
an atypical, dysfunctional phenotype (defined as CD27−CD21lo/−) are
expanded compared to vaccinated healthy controls. This population
expresses high levels of inhibitory receptors, and accordingly exhibits
impaired cytokine production, B cell receptor signaling and differentiation
into plasma cells compared to classical memory B cells.
Preliminary data suggest that immune complexes, known to circulate
in patients with chronic HBV infection, may further suppress B cell
receptor signaling through binding to inhibitory Fc-receptors
preferentially expressed on atypical memory B cells. Atypical
memory B cells with a dysfunctional phenotype are further enriched
within the HBV-infected liver, where they constitute a higher
proportion of the mature B cell pool than in healthy controls.
Conclusion: Overall, these data suggest that chronic antigen
exposure in CHB can drive dysfunction of HBsAg-specific B cells,
that may contribute to the failure of immune control.

StephenW

EASL 2018 SAT-413
功能失调的表面抗原特异性记忆B细胞
在慢性乙型肝炎感染中积累
A. Burton1，L.J.Pallett2，L.Mccoy1，K.Suveizdyte1，O.E. Amin1，Froghi3，
B.R。戴维森3，美国吉尔4，P.A. Blair5，C.Mauri5，N.Pelletier6，M。 Maini1。
1UCL，感染与免疫部，伦敦，英国;
感染与免疫的二维感染，英国伦敦; 3UCL，
英国伦敦肝脏和消化健康研究所; 4Barts
和伦敦免疫生物学中心，伦敦，英国;
英国伦敦医学部5UCL; 6罗氏创新
中心，罗氏制药和早期研究开发，巴塞尔，
瑞士
电子邮件：[email protected]
背景和目标：一个重要而且不足的研究
乙型肝炎（HBV）感染的自然控制的组成部分是
针对HBV表面抗原（HBsAg;
抗-HBs），这是功能性治疗的标志。生产
抗体不足以中和大量的循环
HBsAg表明全球和/或HBsAg特异性可能存在缺陷
记忆B细胞隔室。
方法：使用新型诱饵试剂和16色流式细胞仪，我们
全面分析了全球的表型和功能
和HBsAg特异性B细胞亚群在异质性队列中
慢性HBV感染（CHB）和HBV接种的患者
健康的控制。
结果：我们显示HBsAg特异性B细胞在CHB中可检测到，
尽管在这些患者中缺乏循环抗HBs抗体。
然而，在CHB患者中，HBsAg特异性记忆B细胞具有
一种非典型的，功能失调的表型（定义为CD27-CD21lo - ）
与接种疫苗的健康对照相比扩大。这个人口
表达高水平的抑制性受体，因此表现出来
细胞因子产生受损，B细胞受体信号传导和分化
进入浆细胞相比，经典记忆B细胞。
初步数据表明已知可循环的免疫复合物
在慢性HBV感染的患者中，可能进一步抑制B细胞
受体信号通过与抑制性Fc受体结合
优先在非典型记忆B细胞上表达。非典型的
具有功能障碍表型的记忆B细胞被进一步富集
在HBV感染的肝脏内，它们构成较高的肝脏
成熟B细胞库的比例高于健康对照。
结论：总的来说，这些数据表明慢性抗原
慢性乙型肝炎暴露可导致HBsAg特异性B细胞功能障碍，
这可能会导致免疫控制失败。

齐欢畅

是的