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

Gabriel D. Victora, Tanja A. Schwickert, David R. Fooksman, Alice O. Kamphorst, Michael Meyer-Hermann, Michael L. Dustin, Michel C. Nussenzweig

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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.

Original languageEnglish (US)
Pages (from-to)592-605
Number of pages14
JournalCell
Volume143
Issue number4
DOIs
StatePublished - Nov 12 2010

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Keywords

  • Molimmuno

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Victora, G. D., Schwickert, T. A., Fooksman, D. R., Kamphorst, A. O., Meyer-Hermann, M., Dustin, M. L., & Nussenzweig, M. C. (2010). Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell, 143(4), 592-605. https://doi.org/10.1016/j.cell.2010.10.032