Human germinal centres engage memory and naive B cells after influenza vaccination.
Human germinal centres engage memory and naive B cells after influenza vaccination.
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DOI：
10.1038/s41586-020-2711-0
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发表时间：
2020-10
期刊：
影响因子：
64.8
通讯作者：
Ellebedy AH
中科院分区：
文献类型：
--
作者：
Turner JS;Zhou JQ;Han J;Schmitz AJ;Rizk AA;Alsoussi WB;Lei T;Amor M;McIntire KM;Meade P;Strohmeier S;Brent RI;Richey ST;Haile A;Yang YR;Klebert MK;Suessen T;Teefey S;Presti RM;Krammer F;Kleinstein SH;Ward AB;Ellebedy AH
流感病毒仍然是一个重大的公共卫生威胁。人类季节性流感疫苗接种主要刺激预先存在的记忆B细胞，导致分泌抗体的浆母细胞循环的瞬时波。这种回忆反应有助于“原始抗原罪”，即选择性增强先前暴露于流感病毒抗原的抗体特异性。目前尚不清楚这种疫苗接种是否也可以诱导引流淋巴结（LN）中的生发中心（GC）反应，在那里可以发生募集的B细胞的多样化和成熟。在这里，我们使用超声引导细针穿刺连续采样引流淋巴结，并研究人类流感疫苗接种后GC B细胞反应的动力学和特异性。我们发现，流感疫苗结合GC B细胞可以检测到早在接种后1周。在8名参与者中的3名中，我们在疫苗接种后长达9周检测到疫苗结合GC B细胞。12%至88%的GC B细胞克隆与早期循环浆母细胞中检测到的克隆重叠。这些共享的B细胞克隆具有高频率的体细胞超突变（SHM），并编码广泛交叉反应的单克隆抗体（mAb）。相比之下，仅在GC隔室中检测到的疫苗诱导的B细胞克隆表现出显著较低的SHM频率，并且主要编码菌株特异性mAb，表明幼稚B细胞来源。基于电子显微镜的表位作图显示，这些菌株特异性单克隆抗体中的一些识别早期浆母细胞应答不靶向的表位。我们的研究结果表明，流感病毒疫苗接种的人可以引发GC反应，其中B细胞克隆靶向新的表位更有可能被招募，从而扩大了疫苗诱导的保护性抗体的频谱，对这种快速突变的病原体。
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 plasmablasts. This recall response contributes to “original antigenic sin,” the selective boosting of antibody specificities from prior exposures to influenza virus antigens. 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 occur. 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 naïve 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.
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影响因子：
7.3
作者：
Ellebedy AH;Ahmed R
通讯作者：
Ahmed R
DOI：
10.1073/pnas.1417683112
发表时间：
2015-02-24
影响因子：
11.1
作者：
Gadala-Maria, Daniel;Yaari, Gur;Kleinstein, Steven H.
通讯作者：
Kleinstein, Steven H.
影响因子：
30.5
作者：
Dogan, Ismail;Bertocci, Barbara;Weill, Jean-Claude
通讯作者：
Weill, Jean-Claude
影响因子：
14.9
作者：
Giudicelli, W;Chaume, D;Lefranc, MP
通讯作者：
Lefranc, MP
影响因子：
3
作者：
Camacho C;Coulouris G;Avagyan V;Ma N;Papadopoulos J;Bealer K;Madden TL
通讯作者：
Madden TL