Expression data from germinal center (GC) B cells of Tnfrsf13B wild type, knockout and A144E mutant mice 10 days post immunization with allogenic cells
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PROVIDER: PRJNA757685 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: the goals of this study are to characterize GC B cells elicited by neonatal immunization with HA/CAF01 at the transcriptome level (RNA-seq) and study whether and how maternal antibodies affect GC B cell differentiation in early life Methods: transcriptomic analysis of highly pure GC B cells and the corresponding non-GC B cells isolated from draining lymph nodes of immunized neonatal mice were generated by HiSeq 4000 sequencing, using Illumina Technology. The sequence reads that passed quality filters were analyzed using the package edgeR: the fold-change and the Benjamini-Hochberg corrected p-value thresholds were set to 2 and 0.05 respectively. Main results: 1) we identified the differentially expressed genes (DEGs) in GC B cells versus non-GC B cells in murine neonates born to naive or influenza-immune mothers and observed that the canonical changes reflecting the acquisition of a GC B cell phenotype and state after neonatal immunization are not affected by high titers of maternal antibodies. 2) 39 DEGs distinguished GC B cells elicited in the presence or absence of MatAbs. GC B cells elicited in presence or absence of MatAbs used different VH and Vk genes and showed differences in genes associated with B cell differentiation and isotype switching.
2019-08-13 | GSE126015 | GEO
Project description:Selection of B cells subjected to hypermutation in germinal centres (GC) during T-dependent (TD) antibody responses yields memory cells and long-lived plasma cells that produce high affinity antibodies biased to foreign antigens rather than self-antigens. GC also form in T-independent (TI) responses to polysaccharide antigens but failed selection results in GC involution and memory cells are not generated. To date there are no markers that allow phenotypic distinction of T-dependent and T-independent germinal centre B cells. We have now compared the global gene expression of GC B cells purified from mice immunized with either TD or TI antigens and identified eighty genes that are differentially expressed in TD GC. Experiment Overall Design: QMxB6 F1 mice were immunised with T-independent antigens (NP-Ficoll) or T-dependent antigens (NP-CGG). T-dependent responses were analysed in carrier primed mice and non-carrier primed mice. The kinetics in carrier primed mice are comparable to those of TI-2 antigens, and thus, both of these groups were analysed 4 days after immunization with soluble antigen. The response in non-carrier primed mice peaks later, and was therefore analysed on day 10 after immunization. Germinal centre B cells were MACS enriched and then FACS sorted according to GL-7 and B220 expression. Sorted B cells from the relevant mice were pooled (4-10 mice per sample). Each sample thus contains B cells from different mice, and the replicates are biological, not technical replicates.
2008-06-16 | E-GEOD-8906 | biostudies-arrayexpress
Project description:B cells in the germinal center of the spleen produce antibodies in responses to different antigens. Tnfrsf13b knockout and A144E mice can underlie more aggressive B cells effector responses, possibly at the cost of inadvertent pathogenicity; however, neither the amplitude nor the pathogenicity are simple functions of the amount of antigen-specific IgG produced. We used microarrays to detail the global program of gene expression of germinal center B cells and identified distinct classes of up-regulated genes in the different strains of mice with Tnfrsf13b wild type, knockout, monoallilic or biallec A144E missense mutation.
2021-08-26 | GSE182739 | GEO
Project description:This study seeks to understand the mechanisms behind enhanced lymphomagenesis observed in ImHABCL6/Uchl1 mice compared with ImHABCL6 alone. As the lymphomas arise from germinal center (GC) B-cells, we reasoned that transgenic Uchl1 altered the gene expression patterns in GC B-cells from these animals. We therefore isolated pre-malignant GC B-cells and examined the gene expression patterns to identify pathways affected by the addition of Uchl1. Germinal center B-cells were isolated from from the spleens of ImHABCL6 and ImHABCL6/Uchl1 mutant mice (n= 3 each) after immunization with sheep red blood cells. RNA was extracted and hybridized to affymetrix mouse 430 2.0 arrays.
2016-01-12 | E-GEOD-76706 | biostudies-arrayexpress
Project description:Gene expressions of murine germinal center and naive B cells on Affymetrix platform The experiment include 3 d14 GC B1-8, 3 d14 GC V23 and 4 NaM-CM-/ve samples
2013-03-06 | E-GEOD-44260 | biostudies-arrayexpress
Project description:The MEF2B transcription factor is frequently mutated in germinal center (GC)-derived B-cell lymphomas. Its N-terminal mutations drive lymphomagenesis by escaping interaction with transcriptional repressors, while the function of C-terminal mutations remains to be elucidated. Here, we show that MEF2B C-tail is physiologically phosphorylated at specific residues and phosphorylation at S324 is impaired by lymphoma-associated mutations. Lack of phosphorylation at S324 enhances the interaction of MEF2B with the SWI/SNF chromatin remodeling complex, leading to higher transcriptional activity. In addition, these mutants show an increased protein stability due to impaired interaction with the CUL3/KLHL12 ubiquitin complex. Mice expressing a phosphorylation-deficient lymphoma-associated MEF2B mutant display GC enlargement and develop GC-derived lymphomas, when crossed with Bcl2 transgenic mice. These results unveil converging mechanisms of action for a diverse spectrum of MEF2B mutations, all leading to its dysregulation and GC B-cell lymphomagenesis. These assorted mechanisms provide additional opportunities for the development of targeted therapeutic approaches.
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Project description:Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. It has been proposed that high affinity cells are preferentially selected into this compartment, potentiating the immune response. We used single cell RNA-seq to track the germinal center (GC) development of Ighg2A10 cells, specific for the Plasmodium falciparum circumsporozoite protein (PfCSP). Following immunization with Plasmodium sporozoites we identified 3 populations of cells in the GC light zone. One population expressed a gene signature associated with the initiation of PC differentiation and had an enhanced propensity to form PCs in vitro. Unexpectedly, the estimated affinity of this putative pre-PC population was indistinguishable from cells in the GC generally. This was also true when high- or low-avidity recombinant PfCSP proteins were used as immunogens. Immunization with low-avidity PfCSP did, however, induce increased affinity maturation. Collectively these findings suggest that the initiation of PC development in the GC occurs via an affinity independent process.
2024-01-15 | GSE227370 | GEO
Project description:Long-lived plasma cells (PCs) secrete antibodies that can provide sustained immunity against infection. It has been proposed that high affinity cells are preferentially selected into this compartment, potentiating the immune response. We used single cell RNA-seq to track the germinal center (GC) development of Ighg2A10 cells, specific for the Plasmodium falciparum circumsporozoite protein (PfCSP). Following immunization with Plasmodium sporozoites we identified 3 populations of cells in the GC light zone. One population expressed a gene signature associated with the initiation of PC differentiation and had an enhanced propensity to form PCs in vitro. Unexpectedly, the estimated affinity of this putative pre-PC population was indistinguishable from cells in the GC generally. This was also true when high- or low-avidity recombinant PfCSP proteins were used as immunogens. Immunization with low-avidity PfCSP did, however, induce increased affinity maturation. Collectively these findings suggest that the initiation of PC development in the GC occurs via an affinity independent process.
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Project description:B cells diversify and affinity-mature their antigen receptor repertoire in germinal centers (GC). GC B cells receive help signals during transient interaction with T cells, yet it remains unknown how these transient T-B interactions sustain the subsequent proliferative program of selected B cells. Here we show that the transcription factor AP4 is required for sustained GC B cell proliferation and subsequent establishment of a diverse and protective antibody repertoire. AP4 is induced by c-MYC during the T-B interactions and maintained by T cell-derived IL-21. B cell-specific deletion of AP4 resulted in reduced GC sizes and somatic hypermutation and a failure to control chronic viral infection. These results indicate that AP4 integrates T cell-mediated selection and sustained expansion of GC B cells for humoral immunity. Splenic B cells activated with anti-IgM and CD40L in vitro and germinal center B cells sorted from C57BL/6 mice eight days after immunization with sheep red blood cells (SRBCs) were obtained and genome-wide occupancy of c-MYC, AP4 and active histone marks was profiled by chromatin immunoprecipitation and high-throughput sequencing. Gene expression in MYCâAP4â LZ, MYC+AP4+ LZ, AP4+ DZ, and APâ DZ GC B cells from SRBC-immunized AP4-mCherry / c-MYC-GFP dual reporter mice was profiled by RNA-seq.
2016-08-23 | E-GEOD-80669 | biostudies-arrayexpress
Project description:Germinal centers (GC) arise within B cell follicles upon antigenic challenge. In the dark zones (DZ) of GCs, B cells proliferate and hypermutate their immunoglobulin genes, and mutants with increased affinity are positively selected in the light zone (LZ) to either differentiate into plasma and memory cells, or re-enter the DZ for further refinement. However, the molecular circuits governing GC positive selection are not known. Here, we show that the GC reaction requires the biphasic regulation of c-MYC expression, involving its transient induction during early GC commitment, its repression by BCL6 in DZ B cells, and its re-induction in a subpopulation of positively selected LZ B cells destined to DZ re-entry. Accordingly, acute disruption of MYC function in vivo leads to GC collapse, indicating an essential role in GC physiology. These results have implications for our understanding of GC selection and the role of MYC deregulation in B cell lymphomas. We used microarrays to determine the global gene expression programs that distinguish MYC+ GC B cells from their MYC- negative counterparts. GFPMYC+ and GFPMYC- GC B cell subpopulations were collected by Fluorescence Activated Cell Sorting (FACS) from B cell enriched fractions of splenic mononuclear cell pools of GFPMYC knock-in mice (12 days after SRBC immunization). 5-20ng of total RNA (RIN>9) for each sample was used as a template for linear cDNA amplification (Ovation RNA amplification Kit, NuGen). cDNA was labeled using the Encore Biotin Labeling Kit (NuGen) and hybridized to Affymetrix Mouse 430.2 gene expression arrays.
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