In vivo imaging of germinal centres reveals a dynamic open structure

Tanja A. Schwickert, Randall L. Lindquist, Guy Shakhar, Geulah Livshits, Dimitris Skokos, Marie H. Kosco-Vilbois, Michael L. Dustin () and Michel C. Nussenzweig ()
Additional contact information
Tanja A. Schwickert: Laboratory of Molecular Immunology, and,
Randall L. Lindquist: Laboratory of Molecular Immunology, and,
Guy Shakhar: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Geulah Livshits: Laboratory of Molecular Immunology, and,
Dimitris Skokos: Laboratory of Molecular Immunology, and,
Marie H. Kosco-Vilbois: NovImmune SA, 64 avenue de la Roseraie, 1211 Geneva 4, Switzerland
Michael L. Dustin: Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
Michel C. Nussenzweig: Laboratory of Molecular Immunology, and,

Nature, 2007, vol. 446, issue 7131, 83-87

Abstract: 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 zones1,2,3,4. 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 cells5,6,7. It has been proposed that centrocytes are selected in the light zone on the basis of their ability to bind cognate antigen5,6,7,8. 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 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.

Date: 2007
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DOI: 10.1038/nature05573

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