Primary germinal center-resident T follicular helper cells are a physiologically distinct subset of CXCR5hiPD-1hi T follicular helper cells.
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.
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- Thy-1 Antigens
- T-Lymphocyte Subsets
- T Follicular Helper Cells
- Sphingosine-1-Phosphate Receptors
- Receptors, CXCR5
- Receptors, Antigen, T-Cell
- Programmed Cell Death 1 Receptor
- Mice
- Immunology
- Histocompatibility Antigens Class II
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Thy-1 Antigens
- T-Lymphocyte Subsets
- T Follicular Helper Cells
- Sphingosine-1-Phosphate Receptors
- Receptors, CXCR5
- Receptors, Antigen, T-Cell
- Programmed Cell Death 1 Receptor
- Mice
- Immunology
- Histocompatibility Antigens Class II