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Expression data from murine follicular dendritic cells

ABSTRACT: Germinal centers (GCs) are clusters of activated B cells built on stromal cells known as follicular dendritic cells (FDCs). In the Peyer’s patches (PPs), GCs are chronically induced by bacteria and are the major sites for generation of gut IgA immune responses. Whether FDCs directly contribute to the IgA production in PP GCs is unknown. To investigate the role FDCs in gut immune system, we examined comprehensive gene profiles of FDCs purified from PPs or perypheral lymph nodes (pLNs) with or without immunization. We also tried to reconstitute the PP FDC signature in vitro by pulsed or continuous stimulation of pLN FDCs through TLRs, RARs or simultaneously through TLRs and RARs.

ORGANISM(S): Mus musculus

PROVIDER: GSE19401 | GEO | 2010/07/05

SECONDARY ACCESSION(S): PRJNA121767

REPOSITORIES: GEO

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Expression data from murine follicular dendritic cells

Project description:Germinal centers (GCs) are clusters of activated B cells built on stromal cells known as follicular dendritic cells (FDCs). In the Peyerâs patches (PPs), GCs are chronically induced by bacteria and are the major sites for generation of gut IgA immune responses. Whether FDCs directly contribute to the IgA production in PP GCs is unknown. To investigate the role FDCs in gut immune system, we examined comprehensive gene profiles of FDCs purified from PPs or perypheral lymph nodes (pLNs) with or without immunization. We also tried to reconstitute the PP FDC signature in vitro by pulsed or continuous stimulation of pLN FDCs through TLRs, RARs or simultaneously through TLRs and RARs. The number of samples is as follows; ex vivo naÃ¯ve pLN FDC=3, ex vivo immunized pLN FDC=2, ex vivo PP FDCs=3, in vitro without stimulation=2, in vitro with LPS stimulation for 5 hours=1, in vitro with LPS stimulation for 72h=1, in vitro with Pam2CSK4 (Pam) stimulation for 96h=2, in vitro with retinoic acid(RA) stimulation for 96h=2,in vitro with RA+Pam stimulation for 96h=2. In addition, ex vivo FDCs with or without immunizations were compared (3 samples), or in vitro cultured FDCs with or without various stimulations were compared (6 samples)

2010-07-30 | E-GEOD-19401 | biostudies-arrayexpress

Transcription profiling of mouse primary splenocytes enriched or depleted of follicular dendritic cells to study the events leading to maturation of follicular dendritic cells and lymphoid germinal centers.

Project description:Comparison of follicular dendritic cell-enriched versus -depleted splenocytes. Affinity maturation and Ab class switches occur in lymphoid germinal centers (GCs), in which differentiation and maintenance depend on lymphotoxin (LT) signaling and include differentiation of follicular dendritic cells (FDCs). The events leading to FDC and GC maturation are poorly defined. Using several approaches of functional genomics, we enumerated transcripts affected in mice by suppressing LT receptor (LTR) signaling and/or overrepresented in FDC-enriched GC isolates. Protein expression analysis of 3 of 12 genes both enriched in FDCs and down-regulated by LTR signaling suppression validated them as FDC markers. Functional analysis of one of these three, clusterin, suggests a role as an FDC-derived trophic factor for GC B cells. Hence, the set of genes presented in this study includes markers emanating from LTR signaling and transcripts relevant to GC and FDC function.

2007-09-21 | E-GEOD-2123 | biostudies-arrayexpress

Distinctive Histogenesis and Immunological Microenvironment Based on Transcriptional Profiles of Follicular Dendritic Cell Sarcomas

Project description:Follicular dendritic cell (FDC) sarcomas are rare mesenchymal tumours (MTs) with variable clinical, morphologic and phenotypic characteristics. We investigated the transcriptome of 29 FDC sarcomas and compared it with that of other MTs, microdissected Castleman FDCs, and normal fibroblasts. On unsupervised analysis, FDC sarcoma clustered with microdissected FDCs, distinct from other MTs and fibroblasts. The specific endowment of FDC-related programs in FDC sarcomas emerged by applying a gene signature consisting of 1,289 genes differentially expressed between microdissected FDCs and fibroblasts. Supervised analysis comparing FDC sarcomas with microdissected FDCs and other MTs identified 370 and 2,927 differentially expressed transcripts, respectively, which pathway enrichment analysis mainly ascribed to signal transduction, chromatin organization, and extracellular matrix organization programs. Since the transcriptome of FDC sarcomas retained similarity with that of FDCs, we investigated the immune landscape of FDC sarcoma by applying the CIBERSORT analysis to FDC sarcomas and non-FDC MTs, and demonstrated that FDC sarcomas were enriched in TFH and TREG populations, as confirmed in situ by immunohistochemistry. The enrichment in specific T-cell subsets prompted investigating the mRNA expression of the inhibitory immune receptor PD-1 and of its ligands PD-L1 and PD-L2, which were found to be significantly more expressed in FDC sarcomas as compared with other MTs, a finding also confirmed in situ. We demonstrated for the first time the transcriptional relationship of FDC sarcomas with non-malignant FDCs and their distinction from other MTs. Furthermore, we provided evidence of a peculiar immunological microenvironment associated with FDC sarcomas.

2017-04-07 | GSE90592 | GEO

Peyer’s Patch Germinal Centers Select Innate-like BCRs

Project description:Primary B cell receptor (BCR)/antibody variable region exons are generated by V(D)J recombination with junctional diversification creating immensely diverse antigen contact-encoding CDR3s. While most antigen-driven germinal centers (GCs) are transient, gut microbiota-dependent intestinal Peyer’s patch (PP) GCs are chronic. The nature of chronic PP GC BCR repertoires and somatic hyper-mutation (SHM) patterns has remained enigmatic. To elucidate the physiological repertoire of PP GC BCRs, we developed a high throughput antibody repertoire and SHM assay. Remarkably, PP GCs from different mice expanded public clonotypes, each often with identical IgH CDR3. These CDR3s represent innate-like BCRs that appear much more frequently than expected in naïve B cell repertoire by IGoR modeling, but not frequently enough to enter PP GCs at the observed recurrence without cellular selection. Consistently, some public clonotypes are gut microbiota-dependent and encode antibodies reactive to bacteria glycans, while others are not. SPF fecal transfer to germ-free (GF) mice restored two germ-dependent clonotypes, providing direct evidence for BCR selection. In support of this, we identified recurrently selected SHMs in four of the public clonotypes, demonstrating affinity maturation in chronic PP GCs. Our findings suggest that persistent gut antigens select for innate-like BCR clonotypes to seed chronic PP GCs.

2020-02-21 | GSE140795 | GEO

Neutrophil extracellular traps melt Peyer’s patches following stroke and myocardial infarction

Project description:Sterile tissue injury after stroke causes lymphocyte contraction in lymphoid tissues and may decrease circulating IgA-levels. Intestinal Peyer’s patches (PP) harbor large numbers of IgA+ B cell precursors and plasma cells. Whether and how tissue injury triggers PP-B cell death, thereby mediating IgA-loss, is unknown. We found decreased circulating IgA levels in stroke and myocardial infarction patients. Experimental stroke and myocardial infarction in mice phenocopied the human situation. Decreased plasma and fecal IgA were accompanied by rapid and macroscopic shrinkage of PP caused by substantial losses of PP-resident IgA+ precursors and plasma cells in mice. Tissue injury induced neutrophil activation endowed with the release of toxic neutrophil extracellular traps (NETs). Antibody-mediated or genetically- induced neutrophil loss, digestion of NETs, or inhibition of their release by the Gasdermin D blockade completely prevented lymphocyte loss and PP shrinkage. We also identified NETs in the plasma of stroke and myocardial infarction patients. Hence, tissue injury induces systemic NET-release, which might be targeted to maintain immune homeostasis at mucosal barriers.

2024-02-28 | PXD044644 | Pride

miRNA expression profiling divides follicular dendritic cell sarcomas into two groups, related to fibroblasts and myopericytomas or Castleman's disease

Project description:miRNA expression profiling divides 31 follicular dendritic cell (FDC) sarcomas into two subgroups, one group closely related to microdissected FDCs from Castleman´s disease, the other group closely related to fibroblasts and myopericytomas. miRNA was labeled with the Affymetrix FlashTag Biotin HSR RNA Labeling Kit

2017-06-21 | GSE83994 | GEO

Follicular dendritic cells restrict IL4 availability in germinal centers and foster memory B cell generation

Project description:Germinal centers (GCs) are sites of antibody affinity maturation and memory B cell generation. Follicular dendritic cells (FDCs) form a dense stromal network within GCs, but the full extent of their supportive activity is not understood. Here we showed that FDCs expressed IL4Ra and they reduced IL4 availability in GCs. We used scRNA-seq to examine IL4 actions within the GC and identified a subset of light zone cells marked by high IL4Ra and CD23 and lack of a Myc gene-expression signature. Trajectory inference analysis suggested this population could differentiate into pre-memory and pre-plasma cells. Genetic experiments showed that IL4Ra and STAT6 acted intrinsically to restrain pre-memory B cell generation. By reducing IL4 availability, FDCs enhanced GC B cell selection and fostered memory cell generation. This work suggests that GC FDCs provide a niche that limits bystander IL4 activity, focusing IL4 action on B cells undergoing selection and enhancing memory cell differentiation

2021-09-15 | GSE180920 | GEO

Single-cell transcriptomics of Cxcl13+ LN stromal cells

Project description:Purpose: The goal of this study is to characterise the follicular dendritic cells (FDCs) upon antigen-immunocomplex immunisation. Methods: FACS sorting of Live/Death- Podoplanin+ CD31- CD45- CXCL13-TdTomato+ after LN disgregation of CXCL13-CreTdTomato mice. Mice has been previously immunised with antigen-Ics at different time-points. Cells were loaded into 10x Genomics Chromium Platform, and sequenced using Illumina HiSeq 4000. Conclusions: Our study detects previously identified stromal cell populations and shows the heterogeneity present on the FDCs. We detect 3 different FDC clusters.

2023-06-28 | GSE213254 | GEO

In the aftermath of stroke or myocardial infarction, neutrophil extracellular traps disrupt systemic immunoglobulin production

Project description:Post-injury dysfunction of humoral immunity accounts for infections and poor outcome in cardiovascular diseases. Immunoglobulin A (IgA), the most abundant mucosal antibody is produced by plasma B cells in intestinal Peyer’s patches (PP) and lamina propria. Here, we show that stroke and myocardial ischemia (MI) patients had strongly reduced IgA blood levels. This was phenocopied in experimental mouse models where decreased plasma and fecal IgA were accompanied by rapid and macroscopic shrinkage of PP caused by substantial B cell loss. Stroke/MI triggered neutrophils to release neutrophil extracellular traps (NETs). Depletion of neutrophils, NET-degradation, or blockade of NET-release inhibited PP shrinkage and loss of B cells and IgA in stroke mice. Also, stroke and MI patients had higher amounts of circulating NETs, correlating with reduced IgA levels. Strikingly, stroke patients treated with DNase-I had reduced circulating NETs and stable IgA levels. Our results unveil how tissue-injury-triggered systemic NET release disrupts physiological IgA secretion and how this can be inhibited in patients.

2024-03-17 | GSE254410 | GEO

Characterization of human FDCs reveals regulation of T cells and antigen presentation to B cells [Affymetrix]

Project description:Stromal-derived follicular dendritic cells (FDCs) are essential for germinal centers (GCs), the site where B cells maturate their antibodies. FDCs present native antigen to B cells and maintain a CXCL13 gradient to form the B cell follicle. Yet despite their essential role, the transcriptome of human FDCs remains undefined. Using single-cell RNA sequencing and microarray, we provided the transcriptome of these enigmatic cells as a comprehensive resource. Key genes were validated by flow cytometry and microscopy. Surprisingly, marginal reticular cells (MRCs) rather than FDCs expressed B cell activating factor (BAFF). Furthermore, we found that human FDCs expressed TLR4 and can alter antigen availability in response to pathogen-associated molecular patterns (PAMPs). High expression of PD-L1 and PD-L2 on FDCs activated PD1 on T cells. In addition, we found expression of genes related to T cell regulation, such as HLA-DR, CD40, and others. These data suggest intimate contact between human FDCs and T cells.

2021-08-17 | GSE178271 | GEO

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