人类生发中心在流感疫苗接种后会募集记忆 B 细胞和初始 B 细胞。

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

机构信息

Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.

Interdepartmental Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.

出版信息

Nature. 2020 Oct;586(7827):127-132. doi: 10.1038/s41586-020-2711-0. Epub 2020 Aug 31.

Abstract

Influenza viruses remain a major public health threat. Seasonal influenza vaccination in humans primarily stimulates pre-existing memory B cells, which differentiate into a transient wave of circulating antibody-secreting plasmablasts. This recall response contributes to 'original antigenic sin'-the selective increase of antibody species elicited by previous exposures to influenza virus antigens. It remains unclear whether such vaccination can also induce germinal centre reactions in the draining lymph nodes, where diversification and maturation of recruited B cells can occur. Here we used ultrasound-guided fine needle aspiration to serially sample the draining lymph nodes and investigate the dynamics and specificity of germinal centre B cell responses after influenza vaccination in humans. Germinal centre B cells that bind to influenza vaccine could be detected as early as one week after vaccination. In three out of eight participants, we detected vaccine-binding germinal centre B cells up to nine weeks after vaccination. Between 12% and 88% of the responding germinal centre B cell clones overlapped with B cells detected among early circulating plasmablasts. These shared B cell clones had high frequencies of somatic hypermutation and encoded broadly cross-reactive monoclonal antibodies. By contrast, vaccine-induced B cell clones detected only in the germinal centre compartment exhibited significantly lower frequencies of somatic hypermutation and predominantly encoded strain-specific monoclonal antibodies, which suggests a naive B cell origin. Some of these strain-specific monoclonal antibodies recognized epitopes that were not targeted by the early plasmablast response. Thus, influenza virus vaccination in humans can elicit a germinal centre reaction that recruits B cell clones that can target new epitopes, thereby broadening the spectrum of vaccine-induced protective antibodies.

摘要

流感病毒仍然是一个主要的公共卫生威胁。人类的季节性流感疫苗接种主要刺激预先存在的记忆 B 细胞,这些细胞分化为循环抗体分泌浆母细胞的短暂波。这种回忆反应有助于“原始抗原性错误”-先前暴露于流感病毒抗原引起的抗体种类的选择性增加。目前尚不清楚这种疫苗接种是否也能诱导引流淋巴结中的生发中心反应,在那里可以发生募集 B 细胞的多样化和成熟。在这里,我们使用超声引导的细针抽吸术连续采样引流淋巴结,并研究流感疫苗接种后人类生发中心 B 细胞反应的动态和特异性。在接种疫苗后一周内,就可以检测到与流感疫苗结合的生发中心 B 细胞。在 8 名参与者中的 3 名中,我们在接种疫苗后长达 9 周检测到疫苗结合的生发中心 B 细胞。在反应性生发中心 B 细胞克隆中,有 12%至 88%与早期循环浆母细胞中检测到的 B 细胞重叠。这些共享的 B 细胞克隆具有高频的体细胞超突变,并编码广泛交叉反应的单克隆抗体。相比之下,仅在生发中心隔室中检测到的疫苗诱导的 B 细胞克隆显示出明显较低的体细胞超突变频率,并且主要编码株特异性单克隆抗体,这表明其起源于幼稚 B 细胞。其中一些株特异性单克隆抗体识别的表位不是早期浆母细胞反应的靶标。因此,流感病毒疫苗接种可以在人类中引发生发中心反应,募集可以靶向新表位的 B 细胞克隆,从而扩大疫苗诱导的保护性抗体的谱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c218/7566073/f95e76e5eb08/nihms-1622373-f0005.jpg

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