Gene expression in germinal centre light zone and dark zone cells of high or low affinity
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE94638 | GEO | 2017/03/27
SECONDARY ACCESSION(S): PRJNA371646
REPOSITORIES: GEO
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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.
2017-03-27 | GSE94733 | GEO
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.
2020-03-31 | GSE133743 | GEO
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. All samples were obtained from mouse germinal center (GC) B cells (Cgamma1-cre; YFP, P110*, FOXO1 f/f or PTEN f/f animals). Cells used for microarray analysis were FACS sorted cells.
2015-11-23 | E-GEOD-68043 | biostudies-arrayexpress
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.
2015-11-23 | GSE68043 | GEO
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.
2023-07-06 | GSE212542 | GEO
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.
2023-07-06 | GSE212541 | GEO
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
Project description:Despite the key role that antibodies play in protection against malaria, the cellular processes modulating the acquisition of immunity are not fully understood. Using an infection model of severe malaria, we found that GC B cells strongly upregulate the transcription factor T-bet in response to infection. Expression of T-bet in B cells was required for IgG2c switching but reduced the magnitude of GC B cell responses. RNA-sequencing and flow cytometry analysis revealed that T-bet supports a transcriptional program resulting in a substantial enrichment of the GC dark zone (DZ), thereby significantly influencing DZ/light zone (LZ) polarization. Mice deficient in T-bet in their B cells displayed significantly reduced affinity mutation frequencies in their IghV genes and lower antibody avidity than controls, indicating that T-bet modulates affinity maturation. These results demonstrate that T-bet promotes appropriate GC dynamics, thereby leading to the differentiation of B cells with increased affinity for antigen.
2019-11-11 | GSE120728 | GEO
Project description:Despite the key role that antibodies play in protection against malaria, the cellular processes modulating the acquisition of immunity are not fully understood. Using an infection model of severe malaria, we found that GC B cells strongly upregulate the transcription factor T-bet in response to infection. Expression of T-bet in B cells was required for IgG2c switching but reduced the magnitude of GC B cell responses. RNA-sequencing and flow cytometry analysis revealed that T-bet supports a transcriptional program resulting in a substantial enrichment of the GC dark zone (DZ), thereby significantly influencing DZ/light zone (LZ) polarization. Mice deficient in T-bet in their B cells displayed significantly reduced affinity mutation frequencies in their IghV genes and lower antibody avidity than controls, indicating that T-bet modulates affinity maturation. These results demonstrate that T-bet promotes appropriate GC dynamics, thereby leading to the differentiation of B cells with increased affinity for antigen.
2019-11-11 | GSE120727 | GEO
Project description:Germinal centers (GCs) are the sites of affinity maturation, the process by which antibodies improve their affinity for antigen over time (Cyster and Allen, 2019; De Silva and Klein, 2015; Eisen, 2014; Mesin et al., 2016; Rajewsky, 1996; Shlomchik et al., 2019; Victora and Nussenzweig, 2012). For efficient affinity maturation, GC B cells must cycle between two major transcriptional states, associated with localization of B cells to each of the two microanatomical “zones” of the GC. When in the dark zone (DZ), B cells proliferate vigorously while they mutate their immunoglobulin genes by somatic hypermutation (SHM). After transition to the light zone (LZ), B cells bearing advantageous mutations are selectively driven to clonally expand, based at least in part on their ability to bind and present antigen to GC-resident T follicular helper (Tfh) cells (Victora et al., 2010). Successive cycles of somatic hypermutation and affinity-based selection ultimately enrich for higher-affinity cells in among the GC B cell population, in a process known as cyclic re-entry (MacLennan, 1994; Victora and Nussenzweig, 2012).
2020-12-10 | GSE162182 | GEO