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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.

Type

Journal article

Journal

Cell

Publication Date

11/2010

Volume

143

Pages

592 - 605

Addresses

Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.

Keywords

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