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Publication : Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5(hi)PD-1(hi) T follicular helper cells.

First Author  Yeh CH Year  2022
Journal  Immunity Volume  55
Issue  2 Pages  272-289.e7
PubMed ID  35081372 Mgi Jnum  J:335796
Mgi Id  MGI:6874630 Doi  10.1016/j.immuni.2021.12.015
Citation  Yeh CH, et al. (2022) Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5(hi)PD-1(hi) T follicular helper cells. Immunity 55(2):272-289.e7
abstractText  T follicular helper (Tfh) cells are defined by a Bcl6(+)CXCR5(hi)PD-1(hi) phenotype, but only a minor fraction of these reside in germinal centers (GCs). Here, we examined whether GC-resident and -nonresident Tfh cells share a common physiology and function. Fluorescently labeled, GC-resident Tfh cells in different mouse models were distinguished by low expression of CD90. CD90(neg/lo) GCTfh cells required antigen-specific, MHCII(+) B cells to develop and stopped proliferating soon after differentiation. In contrast, nonresident, CD90(hi) Tfh (GCTfh-like) cells developed normally in the absence of MHCII(+) B cells and proliferated continuously during primary responses. The TCR repertoires of both Tfh subsets overlapped initially but later diverged in association with dendritic cell-dependent proliferation of CD90(hi) GCTfh-like cells, suggestive of TCR-dependency seen also in TCR-transgenic adoptive transfer experiments. Furthermore, the transcriptomes of CD90(neg/lo) and CD90(hi) GCTfh-like cells were enriched in different functional pathways. Thus, GC-resident and nonresident Tfh cells have distinct developmental requirements and activities, implying distinct functions.
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