title: Dynamic signaling by T follicular helper cells during germinal center B cell selection.
abstract: T follicular helper (T(FH)) cells select high-affinity, antibody-producing B cells for clonal expansion in germinal centers (GCs), but the nature of their interaction is not well defined. Using intravital imaging, we found that selection is mediated by large but transient contacts between T(FH) and GC B cells presenting the highest levels of cognate peptide bound to major histocompatibility complex II. These interactions elicited transient and sustained increases in T(FH) intracellular free calcium (Ca(2+)) that were associated with T(FH) cell coexpression of the cytokines interleukin-4 and -21. However, increased intracellular Ca(2+) did not arrest TFH cell migration. Instead, T(FH) cells remained motile and continually scanned the surface of many GC B cells, forming short-lived contacts that induced selection through further repeated transient elevations in intracellular Ca(2+).
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shulman
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Gitlin
authors.affiliation: Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Jason S
authors.initials: JS
authors.lastname: Weinstein
authors.affiliation: Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Begoña
authors.initials: B
authors.lastname: Lainez
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA.
authors.forename: Enric
authors.initials: E
authors.lastname: Esplugues
authors.affiliation: Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA. Howard Hughes Medical Institute (HHMI).
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: Department of Internal Medicine (Rheumatology), School of Medicine, Yale University, New Haven, CT 06520, USA. Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Craft
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute (HHMI). nussen@rockefeller.edu.
authors.forename: Michel C
authors.initials: MC
authors.lastname: Nussenzweig
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D020013:Calcium Signaling / Q000276:immunology*; D018858:Germinal Center / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D007378:Interleukins / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D000098546:Interleukin-21
chemical_list: D000949:Histocompatibility Antigens Class II; D007378:Interleukins; D049452:Green Fluorescent Proteins; D015847:Interleukin-4; D000098546:Interleukin-21