Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5hiPD-1hi T follicular helper cells.

Journal Article (Journal Article)

T follicular helper (Tfh) cells are defined by a Bcl6+CXCR5hiPD-1hi 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. CD90neg/lo GCTfh cells required antigen-specific, MHCII+ B cells to develop and stopped proliferating soon after differentiation. In contrast, nonresident, CD90hi 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 CD90hi GCTfh-like cells, suggestive of TCR-dependency seen also in TCR-transgenic adoptive transfer experiments. Furthermore, the transcriptomes of CD90neg/lo and CD90hi 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.

Full Text

Duke Authors

Cited Authors

  • Yeh, C-H; Finney, J; Okada, T; Kurosaki, T; Kelsoe, G

Published Date

  • February 8, 2022

Published In

Volume / Issue

  • 55 / 2

Start / End Page

  • 272 - 289.e7

PubMed ID

  • 35081372

Pubmed Central ID

  • PMC8842852

Electronic International Standard Serial Number (EISSN)

  • 1097-4180

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2021.12.015


  • eng

Conference Location

  • United States