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

TA Schwickert, GD Victora, DR Fooksman… - Journal of Experimental …, 2011 - rupress.org
Journal of Experimental Medicine, 2011rupress.org
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 …
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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