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Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter
Ist Teil von
Cell, 2010-11, Vol.143 (4), p.592-605
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2010
Quelle
MEDLINE
Beschreibungen/Notizen
The germinal center (GC) reaction produces high-affinity antibodies by random mutation and selective clonal expansion of B cells with high-affinity receptors. The mechanism by which B cells are selected remains unclear, as does the role of the two anatomically defined areas of the GC, light zone (LZ) and dark zone (DZ). We combined a transgenic photoactivatable fluorescent protein tracer with multiphoton laser-scanning microscopy and flow cytometry to examine anatomically defined LZ and DZ B cells and GC selection. We find that B cell division is restricted to the DZ, with a net vector of B cell movement from the DZ to the LZ. The decision to return to the DZ and undergo clonal expansion is controlled by T helper cells in the GC LZ, which discern between LZ B cells based on the amount of antigen captured and presented. Thus, T cell help, and not direct competition for antigen, is the limiting factor in GC selection.
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► Photoactivation reveals phenotypic differences between light and dark zone B cells ► Interzonal migration is bidirectional, with a net vector from dark to light zone ► T cell help triggers B cell return from light to dark zone ► Return to dark zone is accompanied by clonal expansion