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

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

Research output: Contribution to journalArticle

183 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1243-1252
Number of pages10
JournalJournal of Experimental Medicine
Volume208
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

    Fingerprint

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Schwickert, T. A., Victora, G. D., Fooksman, D. R., Kamphorst, A. O., Mugnier, M. R., Gitlin, A. D., & Nussenzweig, M. L. D. (2011). A dynamic T cell-limited checkpoint regulates affinity-dependent B cell entry into the germinal center. Journal of Experimental Medicine, 208(6), 1243-1252. https://doi.org/10.1084/jem.20102477