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

Authors :
Chen-Hao Yeh
Joel Finney
Takaharu Okada
Tomohiro Kurosaki
Garnett Kelsoe
Source :
Immunity
Publication Year :
2022

Abstract

Germinal center T follicular helper (GCTfh) cells are defined by a Bcl6(+)CXCR5(hi)PD-1(hi) phenotype, but only a minor fraction of these reside in 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, non-resident, 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 during TCR-transgenic adoptive transfer experiments. Further, the transcriptomes of CD90(neg/lo) and CD90(hi) GCTfh-like cells were enriched in different functional pathways. Thus, GC-resident and non-resident Tfh cells have distinct developmental requirements and activities, implying distinct functions.

Details

Language :
English
Database :
OpenAIRE
Journal :
Immunity
Accession number :
edsair.doi.dedup.....b1d22d733acfc66632d1b1d285c1288b