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流感疫苗接种后生发中心参与记忆和初始B细胞形成
2020-09-02 16:05

美国华盛顿大学医学院Ali H. Ellebedy研究组发现,人接种流感疫苗后, 生发中心(GC)参与记忆和初始B细胞形成。 2020年8月31日,《自然》在线发表了这一成果。

使用超声引导细针抽吸对引流淋巴结(LN)连续采样,研究人员探究了人接种流感疫苗后GC B细胞反应的动力学和特异性。研究人员发现在疫苗接种1周内可检测到结合流感疫苗的GC B细胞。有八分之三的参与者在疫苗接种9周后仍可以检测到结合疫苗的GC B细胞。应答GC B细胞克隆中有12%至88%与早期循环浆母细胞中检测到的克隆重叠。这些共享的B细胞克隆具有高频的体细胞超突变(SHM),并编码广泛的交叉反应性单克隆抗体(mAb)。

相比之下,仅在GC内检测到的疫苗诱导的B细胞克隆具有明显较低的SHM频率,并且主要编码菌株特异性mAb,表明它来源于原始B细胞。电子显微镜表位作图显示,这些菌株特异性mAb可识别某些早期成浆细胞非靶向的表位。

该研究结果表明,人接种流感病毒疫苗可引发GC反应,更有可能招募针对新型抗原决定簇的B细胞克隆,从而扩大了疫苗诱导的针对快速变异病原体保护性抗体的范围。

据了解,流感仍然是产生公共卫生威胁的原因之一。季节性流感疫苗接种主要会刺激先前存在的记忆B细胞,从而导致循环系统中分泌抗体的成浆细胞短暂生成。这种召唤反应导致“原始抗原罪”,即先前暴露于流感病毒抗原的抗体特异性选择性增强。尚不清楚这种疫苗是否还能在引流LN中诱发生发中心反应,多样和成熟B细胞被招募至引流淋巴结。

附:英文原文

Title: Human germinal centres engage memory and naive B cells after influenza vaccination

Author: Jackson S. Turner, Julian Q. Zhou, Julianna Han, Aaron J. Schmitz, Amena A. Rizk, Wafaa B. Alsoussi, Tingting Lei, Mostafa Amor, Katherine M. McIntire, Philip Meade, Shirin Strohmeier, Rafael I. Brent, Sara T. Richey, Alem Haile, Yuhe R. Yang, Michael K. Klebert, Teresa Suessen, Sharlene Teefey, Rachel M. Presti, Florian Krammer, Steven H. Kleinstein, Andrew B. Ward, Ali H. Ellebedy

Issue&Volume: 2020-08-31

Abstract: Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, leading to a transient wave of circulating antibody-secreting plasmablasts1–3. This recall response contributes to “original antigenic sin,” the selective boosting of antibody specificities from prior exposures to influenza virus antigens4. It remains unclear whether such vaccination can also induce germinal centre (GC) reactions in the draining lymph node (LN) where diversification and maturation of recruited B cells can occur5. Here we used ultrasound-guided fine needle aspiration to serially sample the draining LNs and investigate the dynamics and specificity of GC B cell responses after influenza vaccination in humans. We show that influenza vaccine-binding GC B cells can be detected as early as 1 week after vaccination. In 3 out of 8 participants, we detected vaccine-binding GC B cells up to 9 weeks after vaccination. Between 12% and 88% of the responding GC B cell clones overlapped with those detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation (SHM) and encoded broadly cross-reactive monoclonal antibodies (mAbs). In contrast, vaccine-induced B cell clones detected only in the GC compartment exhibited significantly lower SHM frequencies and predominantly encoded strain-specific mAbs, suggesting a naive B cell origin. Electron microscopy-based epitope mapping revealed that some of these strain-specific mAbs recognized epitopes that were not targeted by the early plasmablast response. Our results indicate that influenza virus vaccination of humans can elicit a GC reaction to which B cell clones targeting novel epitopes are more likely to be recruited, thereby broadening the spectrum of vaccine-induced protective antibodies against this rapidly mutating pathogen.

DOI: 10.1038/s41586-020-2711-0

Source: https://www.nature.com/articles/s41586-020-2711-0

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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