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Gene expression of CpG-activated memory B cells

ABSTRACT: During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27lo subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27hi plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27lo and proliferating CD27hi subpopulations. Our data supported an alternative hypothesis, that CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation.

ORGANISM(S): Homo sapiens

PROVIDER: GSE45113 | GEO | 2013/03/13

SECONDARY ACCESSION(S): PRJNA192906

REPOSITORIES: GEO

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Gene expression of CpG-activated memory B cells

Project description:During the human B cell (Bc) recall response, rapid cell division results in multiple Bc subpopulations. The TLR-9 agonist CpG oligodeoxynucleotide, combined with cytokines, causes Bc activation and division in vitro and increased CD27 surface expression in a sub-population of Bc. We hypothesized that the proliferating CD27lo subpopulation, which has a lower frequency of antibody-secreting cells (ASC) than CD27hi plasmablasts, provides alternative functions such as cytokine secretion, costimulation, or antigen presentation. We performed genome-wide transcriptional analysis of CpG activated Bc sorted into undivided, proliferating CD27lo and proliferating CD27hi subpopulations. Our data supported an alternative hypothesis, that CD27lo cells are a transient pre-plasmablast population, expressing genes associated with Bc receptor editing. Undivided cells had an active transcriptional program of non-ASC B cell functions, including cytokine secretion and costimulation, suggesting a link between innate and adaptive Bc responses. Transcriptome analysis suggested a gene regulatory network for CD27lo and CD27hi Bc differentiation. 18 B cell samples from 6 subjects. From each subject, 3 in vitro B cell populations were isolated: undivided cells, proliferating cells with low CD27 (marker of antibody secretion), proliferating cells with high CD27

2013-03-13 | E-GEOD-45113 | biostudies-arrayexpress

Mus musculus

Project description:Spleen vs CpG-oligodeoxynucleotide Treated B cell

| PRJNA84889 | ENA

Spleen vs CpG-oligodeoxynucleotide Treated B cell

Project description:total RNA from mouse (male c57BL/6) spleen labeled with Cy3 vs total RNA from mouse (male c57BL/6) B cells treated with CpG-oligodeoxynucleotide labeled with Cy5- time course with repeats Keywords: ordered

2003-04-14 | GSE378 | GEO

Genome wide DNA methylation sequencing by XmaI-RRBS resolves breast cancer epigenetic heterogeneity and suggests novel perspectives for personalized therapy

Project description:Aim: To provide a breast cancer (BC) methylotype classification by genome-wide CpG islands bisulfite DNA sequencing. Results: Overall, 6 distinct BC methylotypes were identified. Of these, BC cell lines constitute a separate group extremely highly methylated at the CpG islands. In turn, primary BC samples segregate into two major subtypes, highly and moderately methylated.

2018-11-22 | GSE122799 | GEO

Short and long-term changes in gene expression mediated by the activation of TLR9

Project description:CpG DNA binds to Toll-like receptor 9 to stimulate a strong innate immune response. Despite extensive studies of TLR9 mediated signal transduction, the scope of CpG-induced changes in gene expression is incompletely understood. In particular, the prolonged effects of CpG ODN (oligodeoxynucleotide) on gene activation have not been investigated despite evidence that a single dose of CpG ODN alters immune reactivity for several weeks. This study used gene expression analysis to monitor changes in mRNA levels for 14 days, and identified the genes, pathways, functional groups and regulatory networks triggered in vivo following CpG ODN administration. Two discrete peaks of gene activation (at 3 hr and 5 days) were observed after CpG administration. Both the regulation and function of genes activated during the second peak differed from those triggered shortly after CpG administration. Initial gene up-regulation corresponded to a period when TLR9 ligation stimulated genes functionally associated with the generation of innate and adaptive immune responses (e.g. the NF-kB and B-cell receptor pathways). The second peak reflected processes associated with cell division (e.g., cell cycle and DNA replication & repair). Whereas TNF and IFNG played central roles regulating the first peak of activation, E2F1, E2F2, BRCA1, and HRAS had major impact on the networks controlling the second peak. The complex bimodal pattern of gene expression elicited by CpG ODN administration provides novel insights into the long term effects of CpG DNA on genes associated with immunity and cell proliferation. Data from 4 independent biological replicates/time point (9 time points) and 6 untreated controls were used for all statistical analyses. A reference design was used. Reference cDNA vs. sample cDNA were hybridized to same array.

2010-05-16 | E-GEOD-16465 | biostudies-arrayexpress

Short and long-term changes in gene expression mediated by the activation of TLR9

2010-01-08 | GSE16465 | GEO

RNA-seq analysis with isolated human pancreatic islets treated with human breast cancer cell secreted Evs or control

Project description:Epidemiological evidence has identified an association between breast cancer (BC) and systemic dysregulation of glucose metabolism. However, how BC influences glucose homeostasis remains unknown. Here we show that BC-derived extracellular vesicles (EVs) suppress pancreatic endocrine secretion to systemically reset glucose homeostasis. In pancreatic β-cells, miR-122 delivered in BC-derived EVs targets PKM to suppress glycolysis and ATP-dependent insulin exocytosis. Mice receiving high-miR-122 EVs or bearing BC xenograft tumors, but not those with tumors deficient in EV secretion or miR-122, exhibit suppressed insulin secretion, enhanced endogenous glucose production, impaired glucose tolerance, and hyperglycemia. Compared to non-cancer controls, BC patients have higher levels of EV-encapsulated miR-122 and fasting glucose but lower insulin levels in blood; the miR-122 levels are positively associated with glucose and negatively associated with insulin. This EV-mediated glucose reallocation at the whole-body level may contribute to tumor growth and progression, as well as higher incidence of diabetes in BC patients.

2021-08-01 | GSE173276 | GEO

Transcriptomic analyis of in-vitro plasma cell generation from follicular and marginal zone B cells with cell cycle inhibition via PD0332991 and rapamycin

Project description:Plasma cell differentiation is thought to be tied to cell division. We observe that marginal zone B cells are able to differentiate to plasma cells without completing a single cell division. In order to characterize the transcriptome of plasma cells derrived from un-divided MZ B cells we performed in vitro plasma cell differentiation cultures in the presence of the CDK4/6 inhibitor PD0332991 or rapamycin using Blimp1-GFP reporter follicular and MZ B cells. We report here that these resulting plasma cells from undivided MZ B cells exhibit normal plasma cell gene expression and function in the absence of mitosis.

2021-07-22 | GSE180170 | GEO

Characterization of gene expression in antibody secreting cells

Project description:The CD19 positive antibody secreting cells (ASC) in both bone marrow (BM) have the capacity to provide immune memory in addition to cells traditionally considered long-lived, the CD19-negative BM ASC. We performed flow cytometry (FCM) immunophenotyping, fluorescence-activated cell sorting (FACS) for cell subset isolation, ELISpot assays detecting the isotype of antibody secretion as well as antibodies against vaccine derived antigens, and comparative gene expression analyses of CD19- ASC, CD19+ ASC, CD20- B cells, and CD20+ B cells from BM. The findings may aid in the understanding of the differential cell subsets created through vaccination and lead to improved vaccine strategies and production. FACS sorted tissue B cells and antibody secreting cell subset gene expression.

2018-12-03 | GSE107683 | GEO

Asymmetric cancer cell division regulated by AKT, Reactive Oxygen Species (ROS) high versus ROS low mRNA

Project description:Human tumors often contain slowly proliferating cancer cells that resist treatment but we do not know precisely how these cells arise. We show that rapidly proliferating cancer cells can divide asymmetrically to produce slowly proliferating “G0-like” progeny that are enriched following chemotherapy in breast cancer patients. Asymmetric cancer cell division results from asymmetric suppression of AKT/PKB kinase signaling in one daughter cell during telophase of mitosis. Moreover, inhibition of AKT signaling with small molecule drugs can induce asymmetric cancer cell division and the production of slow proliferators. Cancer cells therefore appear to continuously flux between symmetric and asymmetric division depending on the precise state of their AKT signaling network. This model may have significant implications for understanding how tumors grow, evade treatment, and recur. 3 replicates each of MCF7 Reactive Oxygen Species (ROS) high, HCT116 ROS high, MCF7 ROS low, and HCT116 ROS low.

2011-07-14 | E-GEOD-30465 | biostudies-arrayexpress

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