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J Exp Med. 2011 Jun 6;208(6):1243-52. doi: 10.1084/jem.20102477. Epub 2011 May 16.

A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center.

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


The germinal center (GC) reaction is essential for the generation of the somatically hypermutated, high-affinity antibodies that mediate adaptive immunity. Entry into the GC is limited to a small number of B cell clones; however, the process by which this limited number of clones is selected is unclear. In this study, we demonstrate that low-affinity B cells intrinsically capable of seeding a GC reaction fail to expand and become activated in the presence of higher-affinity B cells even before GC coalescence. Live multiphoton imaging shows that selection is based on the amount of peptide-major histocompatibility complex (pMHC) presented to cognate T cells within clusters of responding B and T cells at the T-B border. We propose a model in which T cell help is restricted to the B cells with the highest amounts of pMHC, thus allowing for a dynamic affinity threshold to be imposed on antigen-binding B cells.

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