In vivo imaging of germinal centres reveals a dynamic open structure
In vivo imaging of germinal centres reveals a dynamic open structure
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DOI：
10.1038/nature05573
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发表时间：
2007-03-01
期刊：
影响因子：
64.8
通讯作者：
Nussenzweig, Michel C.
中科院分区：
文献类型：
--
作者：
Schwickert, Tanja A.;Lindquist, Randall L.;Nussenzweig, Michel C.
生发中心是一种特殊的结构，B 淋巴细胞在其中进行克隆扩增、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 细胞在滤泡中定殖，建立生发中心，并成为快速分裂的生发中心中心母细胞，从而产生暗区(1-4)。中心母细胞产生非增殖性中心细胞，这些细胞被认为会迁移到生发中心的浅色区，其中富含捕获抗原的滤泡树突细胞和 CD4(+) T 细胞(5-7)。有人提出，根据中心细胞结合同源抗原的能力在亮区选择中心细胞(5-8)。然而，尚未对生发中心动力学或生发中心细胞在体内的迁移行为进行研究。在此，我们报告了通过双光子激光扫描显微镜对小鼠淋巴结生发中心 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 细胞都是活动的，并且物理上仅限于生发中心，但在暗区和亮区之间双向迁移。值得注意的是，滤泡 B 细胞是生发中心区室的常客，这表明所有 B 细胞都会扫描生发中心捕获的抗原。与这一观察结果一致，我们发现高亲和力抗原特异性 B 细胞可以被募集到正在进行的生发中心反应中。我们得出的结论是，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 细胞能够参与抗体反应。
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(1-4). 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(5-7). It has been proposed that centrocytes are selected in the light zone on the basis of their ability to bind cognate antigen(5-8). 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 bidirectionally 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.