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In vivo imaging of germinal centres reveals a dynamic open structure

机译：生发中心的体内成像揭示了动态的开放结构

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Germinal centres are specialized structures wherein B lymphocytes undergo clonal expansion, class switch recombination, antibody gene diversification and affinity maturation. Three to four antigen-specific B cells colonize a follicle to establish a germinal centre and become rapidly dividing germinal-centre centroblasts that give rise to dark zones. Centroblasts produce non-proliferating centrocytes that are thought to migrate to the light zone of the germinal centre, which is rich in antigen-trapping follicular dendritic cells and CD4~+ T cells. It has been proposed that centrocytes are selected in the light zone on the basis of their ability to bind cognate antigen. However, there have been no studies of germinal-centre dynamics or the migratory behaviour of germinal-centre cells in vivo. Here we report the direct visualization of B cells in lymph node germinal centres by two-photon laser-scanning microscopy in mice. Nearly all antigen-specific B cells participating in a germinal-centre reaction were motile and physically restricted to the germinal centre but migrated bi-directionally between dark and light zones. Notably, follicular B cells were frequent visitors to the germinal-centre compartment, suggesting that all B cells scan antigen trapped in germinal centres. Consistent with this observation, we found that high-affinity antigen-specific B cells can be recruited to an ongoing germinal-centre reaction. We conclude that the open structure of germinal centres enhances competition and ensures that rare high-affinity B cells can participate in antibody responses.
机译：生殖中心是专门的结构，其中B淋巴细胞经历克隆扩增，类别转换重组，抗体基因多样化和亲和力成熟。三到四个抗原特异性B细胞在卵泡中定居，建立生发中心，并迅速分裂成生发中心的成核细胞，从而形成暗区。中心母细胞产生不增殖的中心细胞，据认为它们会迁移到生发中心的亮区，该中心富含捕获抗原的卵泡树突状细胞和CD4〜+ T细胞。已经提出，根据它们结合同源抗原的能力在轻区选择中心细胞。然而，还没有研究体内生发中心动力学或生发中心细胞的迁移行为。在这里我们报告通过小鼠的双光子激光扫描显微镜在淋巴结生发中心的B细胞的直接可视化。几乎所有参与生发中心反应的抗原特异性B细胞都能够活动，并在物理上局限于生发中心，但在暗区和亮区之间双向迁移。值得注意的是，滤泡性B细胞经常到生发中心区访问，这表明所有B细胞都扫描在生发中心捕获的抗原。与此观察一致，我们发现可以将高亲和力的抗原特异性B细胞募集到正在进行的生发中心反应。我们得出结论，生发中心的开放结构增强了竞争并确保稀有的高亲和力B细胞可以参与抗体反应。

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