Journal
NATURE IMMUNOLOGY
Volume 17, Issue 10, Pages 1197-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3554
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Funding
- Arthritis Foundation
- US National Institutes of Health [5 T32 AR07107, K01AR067892, T32GM07205, F30HL120497, R37AR40072, P30AR053495, R21AR063942]
- Alliance for Lupus Research
- Howard Hughes Medical Institute
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Germinal center (GC) B cells undergo affinity selection, which depends on interactions with CD4(+) follicular helper T cells (T-FH cells). We found that T-FH cells progressed through transcriptionally and functionally distinct stages and provided differential signals for GC regulation. They initially localized proximally to mutating B cells, secreted interleukin 21 (IL-21), induced expression of the transcription factor Bcl-6 and selected high-affinity B cell clones. As the GC response evolved, T-FH cells extinguished IL-21 production and switched to IL-4 production, showed robust expression of the co-stimulatory molecule CD40L, and promoted the development of antibody-secreting B cells via upregulation of the transcription factor Blimp-1. Thus, T-FH cells in the B cell follicle progressively differentiate through stages of localization, cytokine production and surface ligand expression to 'fine tune' the GC reaction.
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