biostudies-literatureZhu FFoundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.)3611https://www.ebi.ac.uk/biostudies/studies/S-EPMC10276816biostudies-literatureUnknown14(1)Follicular helper T (Tfh) cells are essential for germinal center (GC) B cell responses. However, it is not clear which PD-1⁺CXCR5⁺Bcl6⁺CD4⁺ T cells will differentiate into PD-1^hiCXCR5^hiBcl6^hi GC-Tfh cells and how GC-Tfh cell differentiation is regulated. Here, we report that the sustained Tigit expression in PD-1⁺CXCR5⁺CD4⁺ T cells marks the precursor Tfh (pre-Tfh) to GC-Tfh transition, whereas Tigit^-PD-1⁺CXCR5⁺CD4⁺ T cells upregulate IL-7Rα to become CXCR5⁺CD4⁺ T memory cells with or without CCR7. We demonstrate that pre-Tfh cells undergo substantial further differentiation at the transcriptome and chromatin accessNature communicationsSpatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4⁺ T cell fate.PMC10276816T32AI007051AI122842AI133679T32AR069516T32GM008361AI130232AI167986AI116188Xia XHarada YGonzalez-Avalos EChandler KMZhu FSchroeder ARBrown ERSialer DOGreer BDWang YHPipkin MEHu HGetzler AJFigge DKutsch OMcMonigle RJXiao CfalseSpatiotemporal resolution of germinal center Tfh cell differentiation and divergence from central memory CD4⁺ T cell fate.Follicular helper T (Tfh) cells are essential for germinal center (GC) B cell responses. However, it is not clear which PD-1⁺CXCR5⁺Bcl6⁺CD4⁺ T cells will differentiate into PD-1^hiCXCR5^hiBcl6^hi GC-Tfh cells and how GC-Tfh cell differentiation is regulated. Here, we report that the sustained Tigit expression in PD-1⁺CXCR5⁺CD4⁺ T cells marks the precursor Tfh (pre-Tfh) to GC-Tfh transition, whereas Tigit^-PD-1⁺CXCR5⁺CD4⁺ T cells upregulate IL-7Rα to become CXCR5⁺CD4⁺ T memory cells with or without CCR7. We demonstrate that pre-Tfh cells undergo substantial further differentiation at the transcriptome and chromatin access2023-01-01T00:00:00Z2023 Jun2025-04-22T01:59:06.693Z2025-04-05T20:11:50.568ZS-EPMC102768163733054910.1038/s41467-023-39299-3