For the first time, two recent studies capture on film the dynamic behaviour of B cells in germinal centres. These studies bring into question classical models of the germinal-centre response and provide insight into the mechanisms of selection of high-affinity B cells.

Germinal centres are specialized sites within organized lymphoid tissues where B cells bearing high-affinity antibodies are expanded and selected. The classical model of a germinal-centre reaction holds that the dark zone of a germinal centre is established by highly proliferating B cells. These cells then stop proliferating and move to the light zone of the germinal centre, which is rich in antigen-trapping follicular dendritic cells (FDCs) and CD4⁺ T cells, where they undergo selection on the basis of the affinity of their surface antibody for antigen. However, by visualizing the movement of B cells in germinal centres using two-photon laser-scanning fluorescent microscopy, both studies reveal that B cells are highly motile and that movement between the dark and light zones can be bidirectional.

...B cells are highly motile and ... movement between the dark and light zones can be bidirectional.

Reporting in Nature, Nussenzweig, Dustin and colleagues tracked the movement of cells in germinal centres of live mice that had received fluorescently labelled antigen-specific B cells or control polyclonal B cells labelled with a different fluorescent dye. In the presence of their cognate antigen, antigen-specific B cells moved within the confines of the germinal centre at a slower rate, and with more pauses, than control cells. In the light zone, contacts between antigen-specific B cells and antigen-bearing FDCs (and macrophages) were frequent but brief, as if the B cells were scanning antigen by crawling along the FDCs. Surprisingly, naive follicular B cells often entered germinal centres, where they too could scan the antigen on FDCs. Moreover, antigen-specific B cells, when transferred to mice in which germinal centres were well established, could join the pre-existing germinal centres if they expressed a high-affinity receptor.

In Science, Cyster, Okada and colleagues also reported similar observations in both explanted and in vivo lymph nodes. In addition, they noted that cell division can occur in both the dark and light zones and that the dynamic movement of germinal-centre B cells was partially dependent on CXC-chemokine ligand 13 (CXCL13) that is expressed by FDCs. Unlike the interactions between B and T cells early in the immune response, most interactions between germinal-centre B cells and CD4⁺ T cells in the light zone were short-lived. In addition, CD4⁺ T cells seemed to make stable attachments to blebs derived from dying B cells, and the authors proposed that this limited the availability of T-cell help in germinal centres.

So, germinal centres seem to be more dynamic than originally thought, allowing free movement of cells between zones and even the recruitment of cells from outside the germinal centre. The studies indicate that the selection of high-affinity B cells is likely to be an ongoing process, which is regulated by competition for antigen and help from T cells.

Author: Lucy Bird