B cell HVEM interaction with T cell BTLA restrains the help delivered to germinal center B cells
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PROVIDER: PRJNA533828 | ENA |
REPOSITORIES: ENA
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Project description:Gene expression of HVEM-deficient versus WT germinal center (GC) B cells.
2019-06-12 | GSE130095 | GEO
Project description:The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles. To determine whether GC B cells receiving high levels of T cell help show a specific change in gene expression, we compared DZ cells in the G1 phase of the cell cycle from αDEC-OVA and control αDEC-CS treated GCs using a fluorescent ubiquitination-based cell cycle indicator (Fucci-tg). RNA sequencing revealed that T cell-mediated selection produced an increase in gene expression programs associated with the cell cycle, metabolism, including the metabolism of nucleotides, and genes downstream of c-Myc and the E2F transcription factors.
2015-08-12 | E-GEOD-71295 | biostudies-arrayexpress
Project description:The germinal center (GC) is a microanatomical compartment wherein high-affinity antibody-producing B cells are selectively expanded. B cells proliferate and mutate their antibody genes in the dark zone (DZ) of the GC and are then selected by T cells in the light zone (LZ) on the basis of affinity. Here, we show that T cell help regulates the speed of cell cycle phase transitions and DNA replication of GC B cells. Genome sequencing and single-molecule analyses revealed that T cell help shortens S phase by regulating replication fork progression while preserving the relative order of replication origin activation. Thus, high-affinity GC B cells are selected by a mechanism that involves prolonged dwell time in the DZ where selected cells undergo accelerated cell cycles.
2015-08-12 | GSE71295 | GEO
Project description:Germinal center (GC) B cells cycle between two states, the light zone (LZ) and the dark zone (DZ), and in the latter they proliferate and hypermutate their immunoglobulin genes. How this functional transition takes place is still controversial. In this study, we demonstrate that ablation of Foxo1 after GC development led to the loss of the DZ GC B cells and disruption of the GC architecture. Mechanistically, even upon provision of adequate T cell help, Foxo1-deficient GC B cells showed less proliferative expansion than controls. Moreover, we found that the transcription factor BATF was transiently induced in LZ GC B cells in a Foxo1-dependent manner and that deletion of BATF similarly led to GC disruption. Thus, our results are consistent with a model where the switch from the LZ to the DZ is triggered after receipt of T cell help, and suggest that Foxo1-mediated BATF up-regulation is at least partly involved in this switch.
2017-03-21 | GSE93554 | GEO
Project description:Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk-deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.
2024-05-06 | GSE244802 | GEO
Project description:CD4+ T-cell help is required for the generation of CD8+ cytotoxic T lymphocyte (CTL) memory. We here reveal how “help” signals delivered during priming impact memory differentiation of CTLs, as informed by genome-wide analyses. “Help” signals promoted the IL-15-dependent maintenance of central memory (TCM) cells. However, they had a much larger impact on the generation of effector memory (TEM) cells and their gene expression program . CD4+ T-cell help created TEM cells that produced Granzyme B and IFNg after antigen-independent recall with IL-12 and IL-18. Furthermore, “helped” memory CTLs expressed the effector program characteristic of “helped” primary CTLs upon recall with MHC class I-restricted antigen only, due to both epigenetic imprinting and sustained mRNA expression of relevant genes . Thus, CD4+ T-cell help delivered during priming creates CD8+ TEM cells with innate and help-independent recall capacities.
2019-10-23 | GSE135141 | GEO
Project description:We performed DNA methylation (HELP) and gene expression profiling in 17 samples of purified Germinal center B cells (GCBs) and Naive B cells (NBC). We performed supervised analysis using HELP data and defined DNA methylation signature differentiting 2 subgroups of B cvells. Study included purification of human B cells form reactive tonsils, DNA purification and DNA methylation analysis using HELP assay.
2011-08-31 | E-GEOD-31671 | biostudies-arrayexpress
Project description: Not available
| S-EPMC6703922 | biostudies-literature
Project description:We performed DNA methylation (HELP) and gene expression profiling in 17 samples of purified Germinal center B cells (GCBs) and Naive B cells (NBC). We performed supervised analysis using HELP data and defined DNA methylation signature differentiting 2 subgroups of B cvells.
2011-09-01 | GSE31671 | 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. 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