Publication Date:
2014-08-30
Description:
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+).〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519234/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4519234/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shulman, Ziv -- Gitlin, Alexander D -- Weinstein, Jason S -- Lainez, Begona -- Esplugues, Enric -- Flavell, Richard A -- Craft, Joseph E -- Nussenzweig, Michel C -- AI037526-19/AI/NIAID NIH HHS/ -- AI072529-06/AI/NIAID NIH HHS/ -- AI100663-02/AI/NIAID NIH HHS/ -- AR053495-08/AR/NIAMS NIH HHS/ -- AR40072-24/AR/NIAMS NIH HHS/ -- P30 AR053495/AR/NIAMS NIH HHS/ -- R01 AI037526/AI/NIAID NIH HHS/ -- R01 AI072529/AI/NIAID NIH HHS/ -- R01 AR040072/AR/NIAMS NIH HHS/ -- R21 AR063942/AR/NIAMS NIH HHS/ -- T32GM07739/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- New York, N.Y. -- Science. 2014 Aug 29;345(6200):1058-62. doi: 10.1126/science.1257861.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. ; 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. ; Department of Immunobiology, School of Medicine, Yale University New Haven, CT 06520, USA. Howard Hughes Medical Institute (HHMI). ; 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. ; Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA. Howard Hughes Medical Institute (HHMI). nussen@rockefeller.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25170154" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
B-Lymphocytes/*immunology
;
Calcium Signaling/*immunology
;
Germinal Center/*immunology
;
Green Fluorescent Proteins/metabolism
;
Histocompatibility Antigens Class II/*immunology
;
Interleukin-4/immunology
;
Interleukins/immunology
;
Mice
;
Mice, Knockout
;
Molecular Imaging
;
T-Lymphocytes, Helper-Inducer/*immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
