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

Journal article

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: Schwickert, T; Victora, G; Fooksman, DR; Kamphorst, A; Mugnier, MR

• Journal: Journal of experimental medicine
• Volume: 208
• Issue: 6
• Pages: 1243-1252
• Publication date: 2011-06-01
• DOI: 10.1084/jem.20102477
• EISSN: 1540-9538
• ISSN: 0022-1007
• Language: English
• Keywords: Peptides; Cell Proliferation; Photons; Mice, Inbred C57BL; Cell Differentiation; Antigens; Germinal Center; Major Histocompatibility Complex; Mice, Transgenic; Microscopy, Fluorescence; B-Lymphocytes; Mice; Antibody Affinity; Animals; Flow Cytometry; T-Lymphocytes