Thymic B cells promote germinal center-like structures and the expansion of follicular helper T cells in lupus-prone mice
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ABSTRACT:
PROVIDER: PRJNA614005 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11389041_1.fastq.gz | Fastqsanger.gz | |||
| SRR11389041_2.fastq.gz | Fastqsanger.gz | |||
| SRR11389042_1.fastq.gz | Fastqsanger.gz | |||
| SRR11389042_2.fastq.gz | Fastqsanger.gz | |||
| SRR11389043_1.fastq.gz | Fastqsanger.gz |
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Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and immune complex deposition. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the role of this population remains undefined. We analyzed the distribution, function, and properties of thymic B cells in the BWF1 murine model of SLE. We found that B cells proliferate and cluster in germinal center-like structures along with autoantibody-secreting cells in the thymus of diseased-BWF1 mice. These thymic B cells induced the differentiation of follicular helper T cells (TFH). Our data suggest that the accumulation of B cells in the thymus of BWF1 mice results in the formation of germinal center-like structures and the expansion of TFH cells, which may favor the differentiation of autoreactive plasma cells. Therefore, the thymus emerges as a niche supporting the maintenance of the pathogenic humoral response in the development of murine SLE.
2020-03-24 | GSE147359 | GEO
Project description:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the activation of autoreactive T and B cells, autoantibody production, and immune complex deposition in various organs. Previous evidence showed abnormal accumulation of B cells in the thymus of lupus-prone mice, but the role of this population in the progression of the disease remains mostly undefined. Here we analyzed the spatial distribution, function, and properties of this thymic B cell population in the BWF1 murine model of SLE. We found that in diseased animals, thymic B cells proliferate, and cluster in structures that resemble ectopic germinal centers. Moreover, we detected antibody-secreting cells in the thymus of diseased-BWF1 mice that produce anti-dsDNA IgG autoantibodies. We also found that thymic B cells from diseased-BWF1 mice induced the differentiation of thymocytes to follicular helper T cells (TFH). These data suggest that the accumulation of B cells in the thymus of BWF1 mice results in the formation of germinal center-like structures and the expansion of a TFH population, which may, in turn, activate and differentiate B cells into autoreactive plasma cells. Therefore, the thymus emerges as an important niche that supports the maintenance of the pathogenic humoral response in the development of murine SLE.
| S-EPMC7199236 | biostudies-literature
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:Characterization of True Germinal center follicular helper T cells
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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: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:Development of plasma cell-prone germinal center B cells
| PRJNA431808 | ENA
Project description:Human T follicular helper cells seed the germinal center-resident regulatory pool
| PRJNA885886 | ENA
Project description:BXD2 mice spontaneously develop autoantibodies and subsequent glomerulonephritis, offering a useful animal model to study autoimmune lupus. Although initial studies showed a critical contribution of IL-17 and Th17 cells in mediating autoimmune B cell responses in BXD2 mice, the role of follicular helper T (Tfh) cells remains incompletely understood. We found that both the frequency of Th17 cells and the levels of IL-17 in circulation in BXD2 mice were comparable to those of wild-type. By contrast, the frequency of PD-1+ CXCR5+ Tfh cells was significantly increased in BXD2 mice compared with wild-type mice, while the frequency of PD-1+ CXCR5+ Foxp3+ follicular regulatory T (Tfr) cells was reduced in the former group. The frequency of Tfh cells rather than that of Th17 cells was positively correlated with the frequency of germinal center B cells as well as the levels of autoantibodies to dsDNA. More importantly, CXCR5+ CD4+ T cells isolated from BXD2 mice induced the production of IgG from naïve B cells in an IL-21-dependent manner, while CCR6+ CD4+ T cells failed to do so. These results together demonstrate that Tfh cells rather than Th17 cells contribute to the autoimmune germinal center reactions in BXD2 mice.
| S-EPMC4358919 | biostudies-literature
Project description:Follicular T helper (T FH ) cells have emerged as a critical limiting factor for controlling the magnitude of neonatal germinal center (GC) reactions and primary vaccine antibody responses. We compared the functional attributes of neonatal and adult T FH cells at the transcriptomic level and demonstrate that the T FH cell program is well initiated in neonates although the T FH gene-expression pattern (i.e. CXCR5, IL-21, Bcl6, TBK1, STAT4, Ascl2 and c-maf) is largely underrepresented as compared to adult T FH cells. Importantly, we identified a dominant T H2 - bias of neonatal T FH cells, with preferential differentiation toward short-lived pre-T FH effector cells. Remarkably, adjuvantation with CpG-ODNs redirect neonatal pre-T FH cells toward committed GC-T FH cells, as illustrated by increased expression of T FH signature genes and reduced expression of T H2 -related genes.
2019-02-21 | GSE126843 | GEO