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Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter.


ABSTRACT: 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.

SUBMITTER: Victora GD 

PROVIDER: S-EPMC3035939 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter.

Victora Gabriel D GD   Schwickert Tanja A TA   Fooksman David R DR   Kamphorst Alice O AO   Meyer-Hermann Michael M   Dustin Michael L ML   Nussenzweig Michel C MC  

Cell 20101101 4


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 cel  ...[more]

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