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Transcriptome analysis of dark zone (DZ) and light zone (LZ) compartments of Wild type (WT) and SykY317F mice

ABSTRACT: Transcriptome analysis of dark zone (DZ) and light zone (LZ) compartments of Wild type (WT) and SykY317F mice

PROVIDER: PRJNA589087 | ENA |

REPOSITORIES: ENA

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Transcriptome analysis of dark zone (DZ) and light zone (LZ) compartments of Wild type (WT) and SykY317F mice

Project description:Analysis of DZ and LZ compartments in the germinal center of WT and SykY317F mice revealed that Syk degradation regulates the gene expression in the light zone compartment.

2019-11-13 | GSE140282 | GEO

Specialized cell state and spatial compartments within the germinal center dark zone

Project description:Within germinal centers (GCs), complex and highly orchestrated molecular programs must balance proliferation, somatic hypermutation (SHM), class switch recombination (CSR) and selection to both provide effective humoral immunity and to protect against genomic instability and neoplastic transformation. In contrast to this complexity, GC B cells are canonically divided into two principal populations, dark zone (DZ) and light zone (LZ) cells. We now demonstrate that following selection in the LZ, B cells migrate to microniches within the canonical DZ that are sites of ongoing cell division. These proliferating DZ (DZp) cells then transit into the larger DZ to become differentiating DZ (DZd) cells before re-entering the LZ. Multidimensional analysis revealed distinct molecular programs in each population commensurate with observed compartmentization of non-compatable functions. These data provide a new three cell zone model that both orders critical GC functions and reveals essential molecular programs of humoral adaptive immunity.

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Gene expression in germinal centre light zone and dark zone cells

Project description:Gene expression analysis performed on FACS sort purified GC LZ and DZ cells of either high and low affinity to identify unique gene signatures. In order to reveal differences between LZ and DZ independent of affinity, we compared a DZ data set (consisting of high and low affinity samples), to a LZ data set (consisting of high and low affinity samples). Analysis revealed distrinct transcription patterns.

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PI3 Kinase and FOXO1 activity differentially control B cells in the germinal center light and dark zone

Project description:PI3K signaling and FOXO transcription factors play opposing roles at several B cell developmental stages. We show here abundant nuclear FOXO1 expression in the proliferative compartment of the germinal center (GC), its dark zone (DZ), and PI3K activity, downregulating FOXO1, in the GC light zone (LZ), where cells are selected for further differentiation. However, here FOXO1 is expressed in c-Myc+ cells destined for DZ reentry. Upon FOXO1 ablation by genetic means or induction of PI3K activity GCs become devoid of their DZ, due at least partly to the downregulation of the chemokine receptor CXCR4. While this is known to prevent proper cyclic selection of cells expressing high-affinity antibodies, the initiation of immunoglobulin switching is essentially dependent on FOXO1 activity.

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PI3 Kinase and FOXO1 activity differentially control B cells in the germinal center light and dark zone

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Project description:DZ (B220+ IgDlo GL-7+ CD95+CXCR4+CD86lo) or LZ (B220+ IgDlo GL-7+ CD95+CXCR4loCD86+) GC B cells were sorted from male Sle1.yaa lupus mice at 2,4,6 months of age. RNA-seq was employed to assess transcriptional changes in the different GC B cell subsets throughout course of disease.

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Gene expression in germinal centre light zone and dark zone cells of high or low affinity

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Germinal Center Dark Zone harbors ATR-dependent determinants of T-cell exclusion that are also identified in aggressive lymphoma – Visium_FFPE_Spatial_Trasciptomics_project

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LZ and DZ GC B cell throughout lupus

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Project description:Germinal centers (GCs), sites of antibody affinity maturation, are organized into dark (DZ) and light (LZ) zones. Here, we uncovered a B cell intrinsic role for STAT3 in GC DZ and LZ organization. Altered zonal organization of STAT3-deficient GCs dampened GC output of long-lived plasma cells (LL-PCs) but increased memory B cells (MBCs). Tfh-GC B cell interaction drive STAT3 tyrosine 705 and serine 727 phosphorylation in LZ B cells, facilitating their recycling into the DZ. An inducible system confirmed STAT3 is not involved in initiating or maintaining the GC but sustains GC zonal organization by regulating GC B cell recycling. RNAseq and ChIPseq analysis identified genes regulated by STAT3 that are critical for LZ cell recycling and transiting through the DZ proliferation and differentiation phases of the DZ. Thus, STAT3 signaling in B cells controls GC zone organization and recycling, and GC egress of LL-PCs, but negatively regulates MBC output.

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