In vivo imaging of germinal centres reveals a dynamic open structure.
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.
Schwickert
Tanja A
TA
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA.
Lindquist
Randall L
RL
Shakhar
Guy
G
Livshits
Geulah
G
Skokos
Dimitris
D
Kosco-Vilbois
Marie H
MH
Dustin
Michael L
ML
Nussenzweig
Michel C
MC
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002448:Cell Adhesion; D002450:Cell Communication; D002465:Cell Movement; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL