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Germinal Center Dynamics Revealed by Multiphoton Microscopy with a Photoactivatable Fluorescent Reporter
Abstract
SUMMARY The germinal center (GC) reaction produces high-affinity antibodies by random mutation and selective clonal expansion of B cells with high-affinity receptors. However, 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 new transgenic photoactivatable green fluorescent protein (PA-GFP) 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, and that there is a net vector of B cell movement from the DZ to the LZ. The decision to return from the LZ to the DZ and undergo clonal expansion is controlled by T cells, which discern between LZ B cells based on the amount of antigen captured, providing a mechanism for GC selection.
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- Victora, G. D., Schwickert, T. A., Fooksman, D. R., Kamphorst, A. O., Meyer-Hermann, M., Dustin, M. L., & Nussenzweig, M. C.
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- Cell
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- Elsevier BV
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- 143
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