In vivo imaging of germinal centres reveals a dynamic open structure

TA Schwickert, RL Lindquist, G Shakhar, G Livshits… - Nature, 2007 - nature.com
TA Schwickert, RL Lindquist, G Shakhar, G Livshits, D Skokos, MH Kosco-Vilbois, ML Dustin
Nature, 2007nature.com
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 …
Abstract
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.
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