Similar Datasets
Project description:PRMT1 regulates B cell fate after positive selection in the germinal center
| PRJNA445965 | ENA
Project description: Not available
| S-EPMC10266067 | biostudies-literature
Project description:The expression of the Nerve growth factor receptor (NGFR) was described in follicular dendritic cells (FDCs), the major lymphoid stromal cell (LSC) compartment regulating B-cell activation within germinal centers (GCs). However, the role of NGFR in humoral response is not well defined. In this work, we have studied the effect of Ngfr KO in LNs organization and function. Ngfr KO led to spontaneous GC formation and expansion of GC B-cell compartment that were related on Ngfr depletion in non-hematopoietic radioresistant compartment. In agreement, Ngfr KO mice showed alterations in LSC with an increased frequency of FDCs harboring an activated phenotype characterized by the overexpression of CD21/35, MAdCAM-1, and VCAM-1. Moreover, Ngfr KO mice showed GC ectopic location, loss of polarization, impaired high-affinity antibody production, and increased circulating autoantibodies. In addition, Ngfr KO/Bcl2 Tg mice displayed increased levels of autoantibodies, higher incidence of autoimmunity, and decreased overall survival. Our work shows that NGFR maintains GC structure and functionality being involved in the regulation of antibody production and immune tolerance.
2023-12-13 | GSE236511 | GEO
Project description:The germinal center (GC) reaction requires tight regulation of B cell and T follicular helper (Tfh) cell interactions to ensure B cell expansion and antibody affinity maturation, while preventing oncogenesis. However, regulatory mechanisms fine-tuning B-T cell interactions within the GC to prevent aberrant activation and proliferation remain incompletely understood. Here, we identify Siglec-G, the mouse ortholog of human Siglec-10, as an immune checkpoint that restrains the GC by dampening B-T cell interactions. Selective and temporal ablation of Siglec-G on B cells after immunization triggers GC hyperplasia and enhanced plasma cell and antibody output. While Siglec-G is dispensable in B cell receptor-mediated processes, it acts as an intrinsic inhibitory receptor of B-T cell interactions in the GC, ultimately limiting Myc and mTORC activation within positively selected GC B cells. Trans interactions of Siglec-G and its glycan ligands on Tfh likely contribute in fine-tuning the strength of bidirectional signaling following contact between GC B cells and Tfh cells. This interaction is further reinforced by glycan remodeling that occurs in the GC, resulting in concurrent decreased in glycan ligands on GC B cells and increased in glycan ligands on Tfh. Moreover, APEX2-based proximity labeling revealed several candidate Siglec-G/10 binding partners on T cells, including BTLA, CD6, and Slamf6, which are known negative regulators of Tfh cell activation. Taken together, our findings identified that Siglec-G acts as a GC checkpoint receptor, restricting B cell proliferation by tuning T cell help following B-T cell interactions.
2026-05-27 | GSE333139 | GEO
Project description:Analysis of the gene expression profile between MYC positive and MYC negative germinal center B-cells. Total RNA isolated from MYC positive and MYC negative GC B-cells, isolated by FACS from 10 day sheep red blood cell immunized mice MycEGFP (a Myc reporter allele, in which a MYC-EGFP fusion protein (MYCEGFP) is expressed from the endogenous Myc locus, Huan, CY et al Eur J Immunol 2008)
2012-09-11 | E-GEOD-39443 | biostudies-arrayexpress
Project description:Systemic autoimmunity is driven by the production of pathogenic autoantibodies that can arise from germinal centers (GCs). Typically, B cells that acquire autoreactivity following somatic hypermutation in the GC die of neglect, but in autoimmunity these autoreactive clones still receive T cell help, driving aberrant selection. GC B cells cycle between the dark zone (DZ), where proliferation and mutation occur, and the light zone (LZ) where selection occurs. Temporal assessment comparing GCs from mice with chronic infection or lupus revealed a shared accumulation of LZ B cells while lupus GC B cells had a unique reduction in proliferation and a progressive loss of MYC and FOXO1 in lupus. This loss in proliferative capacity coincided with a reduction in B cell receptor repertoire diversity and mutational burden. Furthermore, we identified persistent dominant GC B cell clones associated with an expansion in plasma cell differentiation throughout disease. Together, our findings suggest that lupus disease progression is characterized by an inability for proper LZ selection, preventing zonal recycling, thereby driving the permissive selection and differentiation of autoreactive B cells.
2024-11-18 | GSE252246 | GEO
Project description:We used RNA sequencing to characterize gene expression of Ly75+/+ B1-8hi and Ly75-/- B1-8hi B cells from the germinal center light zone (LZ) 12 h after forcing positive selection of the Ly75+/+ population with anti-DEC205-OVA.
2017-05-25 | GSE98778 | GEO
Project description:Compared with naïve B cells, the B cell receptor (BCR) signal in germinal center (GC) B cells is attenuated; however, the significance of this signaling attenuation has not been well defined. Here, to investigate the role of attenuation of BCR signaling, we employed a Csk mutant mouse model in which Csk-deficiency in GC B cells resulted in augmentation of net BCR signaling with no apparent effect on antigen presentation. We found that Csk is required for GC maintenance and efficient antibody affinity maturation. Mechanistically, ROS-induced apoptosis was exacerbated concomitantly with mitochondrial dysfunction in Csk-deficient GC B cells. Hence, our data suggest that attenuation of the BCR signal restrains hyper-ROS production, thereby protecting GC B cells from apoptosis and contributing to efficient affinity maturation.
2024-05-06 | GSE244802 | GEO
Project description:In this work we illustrate the power of coupling single cell analysis of transcriptional states with somatic hypermutation of germinal center B cells to reveal unanticipated roles of metabolic programs in the positive selection. We use massively parallel 5'-end scRNA-seq to simultaneously capture transcriptome states and mutation profiles of IgH variable genes in individual cells. Our computational analyses reveal that the OXPHOS module is enhanced in GC B cells undergoing positive selection in response to different antigens. Through deleting the Cox10 gene, which encodes a cytochrome oxidase assembly factor, specifically in GC B cells, we demonstrate that OXPHOS activity is required for cell division and positive selection. Furthermore, we show that chemical augmentation of OXPHOS activity facilitates the positive selection of GC B cells in vivo. Our findings therefore reveal that tuning of OXPHOS activity by increased affinity BCRs is critical for clonal expansion and positive selection.
2021-04-16 | GSE154634 | GEO
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.
2024-08-26 | PXD043998 | Pride