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

J Exp Med. 2011 Jun 6;208(6):1243-52. doi: 10.1084/jem.20102477. Epub 2011 May 16.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibody Affinity / immunology
  • Antigens / chemistry
  • B-Lymphocytes / cytology*
  • B-Lymphocytes / immunology
  • Cell Differentiation
  • Cell Proliferation
  • Flow Cytometry / methods
  • Germinal Center / metabolism*
  • Major Histocompatibility Complex
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence / methods
  • Peptides / chemistry
  • Photons
  • T-Lymphocytes / cytology*
  • T-Lymphocytes / immunology


  • Antigens
  • Peptides