TY - JOUR
T1 - A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center
AU - Schwickert, Tanja A.
AU - Victora, Gabriel D.
AU - Fooksman, David R.
AU - Kamphorst, Alice O.
AU - Mugnier, Monica R.
AU - Gitlin, Alexander D.
AU - Nussenzweig, Michael L.Dustin
PY - 2011/6
Y1 - 2011/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79958255209&partnerID=8YFLogxK
U2 - 10.1084/jem.20102477
DO - 10.1084/jem.20102477
M3 - Article
C2 - 21576382
AN - SCOPUS:79958255209
SN - 0022-1007
VL - 208
SP - 1243
EP - 1252
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 6
ER -