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

2011; Rockefeller University Press; Volume: 208; Issue: 6 Linguagem: Inglês

10.1084/jem.20102477

1540-9538

Tanja A. Schwickert, Gabriel D. Victora, David Fooksman, Alice O. Kamphorst, Monica R. Mugnier, Alexander D. Gitlin, Michael L. Dustin, Michel C. Nussenzweig,

Immune Cell Function and Interaction

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.