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Abstract：
Germinal centers (GC) are microanatomical lymphoid structures where affinity-matured memory B cells and long-lived bone marrow plasma cells are primarily generated. It is unclear how the maturation of B cells within the GC impacts the breadth and durability of B cell responses to influenza vaccination in humans. We used fine needle aspiration of draining lymph nodes to longitudinally track antigen-specific GC B cell responses to seasonal influenza vaccination. Antigen-specific GC B cells persisted for at least 13 wk after vaccination in two out of seven individuals. Monoclonal antibodies (mAbs) derived from persisting GC B cell clones exhibit enhanced binding affinity and breadth to influenza hemagglutinin (HA) antigens compared with related GC clonotypes isolated earlier in the response. Structural studies of early and late GC-derived mAbs from one clonal lineage in complex with H1 and H5 HAs revealed an altered binding footprint. Our study shows that inducing sustained GC reactions after influenza vaccination in humans supports the maturation of responding B cells.
摘要：
生发中心（GC）是微解剖淋巴结构，主要产生亲和力成熟的记忆B细胞和长寿命的骨髓浆细胞。目前尚不清楚GC内B细胞的成熟如何影响人类B细胞对流感疫苗接种反应的广度和持久性。我们使用引流淋巴结的细针抽吸术纵向追踪抗原特异性GCB细胞对季节性流感疫苗接种的反应。抗原特异性GCB细胞在接种疫苗后至少持续了13周7个个体中的2个。与响应中早期分离的相关GC克隆型相比，源自持续GCB细胞克隆的单克隆抗体（mAb）对流感血凝素（HA）抗原的结合亲和力和广度增强。来自与H1和H5HA复合的一个克隆谱系的早期和晚期GC衍生的mAb的结构研究揭示了结合足迹的改变。我们的研究表明，在人类接种流感疫苗后诱导持续的GC反应支持响应B细胞的成熟。
