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Transcriptomic analyis follicular and marginal zone B ells after in vivo Notch2 blockade.

ABSTRACT: Marginal zone B cells which make rapid mitosis-independent plasma cell responses are dependent on Notch2 signaling for their generation and maintenance. In order to determine the effect of ongoing Notch signaling on the maintenance of the MZ transcriptome, we performed RNA-seq on MZ and follicular B cells after 12, 24 and 48 hours of in vivo Notch2 antibody blockade

ORGANISM(S): Mus musculus

PROVIDER: GSE180172 | GEO | 2021/07/22

REPOSITORIES: GEO

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

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Comparison of gene expression profiles between mouse follicular and marginal zone B-cells

Project description:Immature B cells in spleens of mouse and human differentiate into at least two subsets of mature B cells, the follicular (FO) B cells and the marginal zone (MZ) B cells, but functions, maturation and other properties of these cells are largely unknown. To solve these questions, in this study, we performed transcriptome analyses of FO and MZ B cells sorted from spleens of normal unimmunized mice using gene chips. By comparison of gene expression profiles between FO and MZ B cells, we identified 1226 genes that are expressed higher in FO B cells than in MZ B cells. On the other hand, 1734 genes were found to be expressed higher in MZ B cells than in FO B cells. We noticed that some of differentially expressed genes have been reportedly characterized in FO and MZ B cells, suggesting the reliability of the analysis. By using FACS analyses, we confirmed that CD36, CD68, and CD49e are expressed on MZ B-cells but not on FO B-cells. These results revealed new phenotypic and functional properties of FO and MZ B cells, and set a molecular basis for further studying differentiation and functions of these mature B cells. Keywords: Comparison of gene expression profiles between mouse follicular and marginal zone B-cells

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IKKα is essential for the development and maintenance of Marginal zone and Follicular B cells

Project description:IKKα kinase is essential for the B cell maturation and secondary lymphoid organ development. In the current study, we evaluated the role of IKKα in the marginal zone and follicular B lymphocyte development by genetically deleting IKKα from the B cell lineage using CD19-Cre mice. The loss of IKKα did not affect the normal development of early B cell progenitors. However, a significant decline was observed in the percentage of immature B lymphocytes, mature marginal zone and follicular B cells along with a severe disruption of splenic marginal and follicular B cell zones. A gene expression analysis performed on the RNA extracted from the newly formed B cells (B220+IgMhi) revealed that IKKα deficiency produces significant changes in the expression of genes involved in MZ and FO B lymphocyte survival, homing and migration. And several among those genes identified belong to G protein family. Specifically, we validated the upregulated expression of regulator of G protein signaling 13 (RGS13), which is a GTPase activating protein (GAP) that negatively regulates G protein signaling and impede B cell migration. Likewise, promigratory B lymphocyte receptor, the sphingosine-1-phosphate receptor 3 (SIPR3) that couple to Gαi showed significantly reduced expression. In addition, an in silico analysis of gene product interactions revealed NF-κB signaling pathways to be a major gene regulating networks perturbed with IKKα deletion. Taken together, this study reveals IKKαNF-κB and G protein signaling axis to be central for the MZ and FO B cells survival, maintenance, homing and migration.

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