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

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.

Pubmed ID: 21074050

Authors

  • Victora GD
  • Schwickert TA
  • Fooksman DR
  • Kamphorst AO
  • Meyer-Hermann M
  • Dustin ML
  • Nussenzweig MC

Journal

Cell

Publication Data

November 12, 2010

Associated Grants

  • Agency: NCI NIH HHS, Id: CA009161-34
  • Agency: NIAID NIH HHS, Id: P01 AI071195
  • Agency: NIAID NIH HHS, Id: R01 AI072529
  • Agency: NIAID NIH HHS, Id: R01 AI072529
  • Agency: NIAID NIH HHS, Id: R01 AI072529-04
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Antigens
  • B-Lymphocytes
  • Female
  • Germinal Center
  • Humans
  • Immunity, Humoral
  • Lymph Nodes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence, Multiphoton
  • Spleen
  • T-Lymphocytes