title: A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Tanja A
authors.initials: TA
authors.lastname: Schwickert
authors.forename: Gabriel D
authors.initials: GD
authors.lastname: Victora
authors.forename: David R
authors.initials: DR
authors.lastname: Fooksman
authors.forename: Alice O
authors.initials: AO
authors.lastname: Kamphorst
authors.forename: Monica R
authors.initials: MR
authors.lastname: Mugnier
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Gitlin
authors.forename: Michael L
authors.initials: ML
authors.lastname: Dustin
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D000941:Antigens / Q000737:chemistry; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002454:Cell Differentiation; D049109:Cell Proliferation; D005434:Flow Cytometry / Q000379:methods; D018858:Germinal Center / Q000378:metabolism*; D008285:Major Histocompatibility Complex; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods; D010455:Peptides / Q000737:chemistry; D017785:Photons; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology
chemical_list: D000941:Antigens; D010455:Peptides