Characterization of True Germinal center follicular helper T cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA612831 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11311300.fastq.gz | Fastqsanger.gz | |||
| SRR11311301.fastq.gz | Fastqsanger.gz | |||
| SRR11311302.fastq.gz | Fastqsanger.gz | |||
| SRR11311303.fastq.gz | Fastqsanger.gz | |||
| SRR11311304.fastq.gz | Fastqsanger.gz |
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Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. This SuperSeries is composed of the following subset Series: GSE21379: Expression Data from WT and Sh2d1a-/- in vivo follicular helper CD4 T cells (TFH) versus non follicular helper CD4 T cells (non-TFH) GSE21380: Expression Data from in vivo Tfh vs GC Tfh vs non-Tfh Refer to individual Series
2010-04-28 | E-GEOD-21381 | biostudies-arrayexpress
Project description:Despite interest in T follicular helper (TFH) cell development and function, differences between TFH cells resident in germinal centers (GCs) and phenotypically similar, non-resident TFH cells are unclear. Both TFH subsets share the Bcl6+FoxP3−CXCR5hiPD-1hi phenotype but we show that only GC resident TFH cells express S1pr2 and lose CD90 expression. Whereas immunization elicits CD90neg/lo GCTFH and CD90hi GCTFH-like cells similarly, these TFH subsets have distinct properties. CD90neg/lo GCTFH cells require MHCII+ B cells to develop and once formed, do not proliferate. CD90hi GCTFH-like cells are generated in the absence of B cells and remain mitotically active. The Tcrβ repertoires of both TFH types are initially shared but with time, Tcrβ usage in CD90hi GCTFH-like cells substantially diverges by DC-driven proliferation. Transcriptome analysis shows CD90neg/lo GCTFH to be specialized for vesicle transport and exocytosis while gene expression in CD90hi GCTFH-like cells is linked to cell activation, proliferation and migration.
2020-03-17 | GSE147035 | GEO
Project description:The Germinal center is a dynamic microenvironment wherein B cells expressing high affinity antibody variants produced by hypermutation are selected for clonal expansion by limiting numbers of T follicular helper cells. Although a great deal is known about the mechanisms that control B cell selection in the germinal center, far less is understood about the clonal behavior of the T follicular helper cells that regulate this process. Here we report on the dynamic behavior of clones of T follicular helper cells during the germinal center reaction. We find that like germinal center B cells, T follicular helper cells undergo antigen dependent selection during the germinal center reaction resulting in differential proliferative expansion and contraction. Increasing the amount of antigen presented in the germinal center leads to increased T follicular cell division. Competition between T follicular helper cell clones is mediated by T cell receptor affinity for peptide-MHC ligand. Higher affinity T cells expanding preferentially in the germinal center show increased expression of genes downstream of the T cell receptor, genes required for metabolic reprogramming, cell division and cytokine production. These dynamic changes lead to dramatic remodeling of the functional T follicular cell repertoire during the germinal center reaction.
2020-03-19 | GSE147182 | GEO
Project description:Human T follicular helper cells seed the germinal center-resident regulatory pool
| PRJNA885886 | ENA
Project description:Productive B cell responses are critical to protect a host from infection. The spleen and lymph nodes are populated by resting follicular B cells, which can enter germinal centers upon antigen encounter. Once in the germinal center, B cells migrate between the dark and light zones, where they undergo somatic hypermutation and selection, respectively. While germinal center B cells have been studied, an intense molecular understanding of these cells/subsets (and the differences between them) is lacking.
2020-04-06 | PXD015524 | Pride
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. This SuperSeries is composed of the SubSeries listed below.
2010-04-20 | GSE21381 | GEO
Project description:CD4 T cell help is critical for both the generation and maintenance of germinal centers, and T follicular helper (TFH) cells are the CD4 T cell subset required for this process. SAP (SH2D1A) expression in CD4 T cells is essential for germinal center development. However, SAP-deficient mice have only a moderate defect in TFH differentiation as defined by common TFH surface markers. CXCR5+ TFH cells are found within the germinal center as well as along the boundary regions of T/B cell zones. Here we show that germinal center associated T cells (GC TFH) can be identified by their co-expression of CXCR5 and the GL7 epitope, allowing for phenotypic and functional analysis of TFH and GC TFH populations. Here we show GC TFH are a functionally discrete subset of further polarized TFH cells, with enhanced B cell help capacity and a specialized ability to produce IL-4 in a TH2-independent manner. Strikingly, SAP-deficient mice have an absence of the GC TFH subset and SAP- TFH are defective in IL-4 and IL-21 production. We further demonstrate that SLAM (Slamf1, CD150), a surface receptor that utilizes SAP signaling, is specifically required for IL-4 production by GC TFH. GC TFH cells require IL-4 and IL-21 production for optimal help to B cells. These data illustrate complexities of SAP-dependent SLAM family receptor signaling, revealing a prominent role for SLAM receptor ligation in IL-4 production by germinal center CD4 T cells but not in TFH and GC TFH differentiation. Analysis of in vivo antigen-specific (LCMV-specific, SMARTA TCR transgenic) WT and Sh2d1a-/- follicular helper CD4 T cells (CXCR5high),versus non-follicular helper CD4 T cells (CXCR5low), eight days after viral infection.
2010-04-28 | E-GEOD-21379 | biostudies-arrayexpress
Project description:Neonatal T follicular helper cells are lodged in a pre-T follicular helper stage favoring innate over adaptive germinal center responses
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Project description:FOXP3+ T follicular regulatory cells (Tfrs) control germinal center (GC) responses by steering antibody formation away from self-reactivity and toward microbe/vaccine recognition. As originally described, murine Tfr cells descend exclusively from thymically-derived, self-antigen recognizing, T regulatory cells (Tregs), but newer animal models suggest vaccine-recognizing T follicular helper (Tfh) cells can assume regulatory roles as GCs mature. To test the hypothesis that the human Tfr pool is heterogenous in function and provenance, we used paired TCRVA and TCRVB sequencing to distinguish tonsillar Tfr cells clonally related to the natural Tregs (nTfr) from those induced from Tfh cells (iTfr). Through in silico predictions and in vitro tonsillar organoid lineage tracking, we identified a Tfh to iTfr developmental trajectory that passed through a distinct CD25hiBLIMP1+FOXP3- transitional stage. The genes and proteins that iTfr and nTfr cells express differentially were utilized as handles to precisely pinpoint the in situ locations of cells from each subset via multi-plex microscopy and to establish divergent functional adaptations. In total, we characterize human iTfr cells as a GC-resident CD38+ Tfr subset that descend from Tfh lineage cells to gain suppressive qualities while retaining their capacity for GC B-cell help.
2023-02-23 | GSE214572 | GEO
Project description:Here we show a newly identified human Innate Lymphoid Cell population present in the follicles of tonsils and lymph nodes termed follicular regulatory ILCs (ILCFR). ILCFR have a distinct phenotype and transcriptional program when compared to other defined ILCs. Surprisingly, ILCFR inhibit the ability of follicular helper T (Tfh) cells to provide B cell help. The localization of ILCFR to the germinal centers suggests these cells may interfere with germinal center B cell (GC-B) and germinal center Tfh cell (GC-Tfh) interactions through the production of transforming growth factor beta (TGF-b). Intriguingly, under conditions of impaired GC-Tfh-GC-B cell interactions, such as human immunodeficiency virus (HIV) infection, the frequency of these cells is increased. Overall, we predict a role for ILCFR in regulating GC-Tfh-GC-B cell interactions and propose they expand in chronic inflammatory conditions.
2021-05-20 | GSE168407 | GEO