Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter.
Cell, 2010/11/12;143(4):592-605.
Victora GD[1], Schwickert TA, Fooksman DR, Kamphorst AO, Meyer-Hermann M, Dustin ML, Nussenzweig MC
Affiliations
PMID: 21074050DOI: 10.1016/j.cell.2010.10.032
Impact factor: 66.85
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.
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
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