Similar Datasets
Project description:Gene expression by RNAseq in murine germinal centers induced by SRBC in RagC T89N mice (YRT codes) and RNAseq in murine B220+ from VavVPBcl2/RagC S74C and VavVPBcl2/RagC +/+ lymphomas Follicular Lymphoma (FL) is an incurable B cell malignancy derived from germinal center (GC) B cells. The RRAGC gene, encoding a GTPase that links cellular nutrient sufficiency with the activation of mechanistic target of rapamycin complex 1 (mTORC1) is mutated in 15% of FL patients, but its impact in B cell functions and lymphomas is unexplored. Endogenous expression of Rragc mutant variants in B lymphocytes from novel knock-in strains of mice resulted in a partial insensitivity of mTORC1 to nutrient deprivation. A mild, but not a full-blown activation of the nutrient signaling pathway enhanced B cell activation and the GC response, suppressed apoptosis, and accelerated lymphomagenesis. Moreover, murine RRAGC mutant FL showed selective vulnerability to pharmacological inhibition of mTORC1. This moderate increase in nutrient signaling synergized with paracrine cues from the supportive T cell microenvironment that activate mTORC1 via the PI3K-Akt axis to promote B cell activation. Hence, RRAGC mutations sustained experimental GCs and murine and human FL in the presence of decreased T cell support. Moreover, mutations in RRAGC in human FLs are mutually-exclusive with mutations that result in increased abundance of T helper cells, consistent with functional redundancy between those pathways. Taken together, our results support a model in which activating mutations in the nutrient signaling pathway foster lymphomagenesis by corrupting a nutrient-dependent control of mTORC1-activating paracrine signals from the T cell microenvironment
2019-07-15 | GSE125394 | GEO
Project description:Gene expression by RNAseq in murine B220+ from VavP-Bcl2/RagC Q119L/+ and VavP-Bcl2/RagC +/+ lymphomas
2021-07-13 | GSE173619 | GEO
Project description:Gene expression profiling in RagC Q119L murine germinal centre B cells and B220+ lymphoma cells
| PRJNA727837 | ENA
Project description:Gene expression by RNAseq in murine RagC Q119L/+ and RagC +/+ germinal centre B cells
2021-07-13 | GSE174003 | GEO
Project description:Gene expression profiling in RagC T89N germinal center B cells and RagC S74C murine B220+ lymphoma cells
| PRJNA516208 | ENA
Project description:Gene expression profiling in RagC Q119L murine B220+ lymphoma cells
| PRJNA726407 | ENA
Project description:Gene expression profiling in RagC Q119L germinal centre B cells
| PRJNA727841 | ENA
Project description:Gene expression by RNAseq in murine germinal center B cells induced by SRBC in RagC S74C mice Follicular Lymphoma (FL) is an incurable B cell malignancy derived from germinal center (GC) B cells. The RRAGC gene, encoding a GTPase that links cellular nutrient sufficiency with the activation of mechanistic target of rapamycin complex 1 (mTORC1) is mutated in 15% of FL patients, but its impact in B cell functions and lymphomas is unexplored. Endogenous expression of Rragc mutant variants in B lymphocytes from novel knock-in strains of mice resulted in a partial insensitivity of mTORC1 to nutrient deprivation. A mild, but not a full-blown activation of the nutrient signaling pathway enhanced B cell activation and the GC response, suppressed apoptosis, and accelerated lymphomagenesis. Moreover, murine RRAGC mutant FL showed selective vulnerability to pharmacological inhibition of mTORC1. This moderate increase in nutrient signaling synergized with paracrine cues from the supportive T cell microenvironment that activate mTORC1 via the PI3K-Akt axis to promote B cell activation. Hence, RRAGC mutations sustained experimental GCs and murine and human FL in the presence of decreased T cell support. Moreover, mutations in RRAGC in human FLs are mutually-exclusive with mutations that result in increased abundance of T helper cells, consistent with functional redundancy between those pathways. Taken together, our results support a model in which activating mutations in the nutrient signaling pathway foster lymphomagenesis by corrupting a nutrient-dependent control of mTORC1-activating paracrine signals from the T cell microenvironment
2019-07-15 | GSE125393 | GEO
Project description:Although all murine MDSCs are defined as Gr1+CD11b+, their true immunophenotype remains elusive. In this study, we found murine Gr1+CD11b+ cells can be divided into two subsets: Gr1+CD11b+B220- and Gr1+CD11b+B220+, especially in the spleen tissues. Unlike the dominant B220- subset, the B220+ subpopulation was not induced by tumor in vivo. Moreover, Gr1+CD11b+B220+ cells from tumor-bearing mice spleens were unable to induce arginase 1 and inducible nitric oxide synthase expression, inhibit T cell proliferation, or promote tumor growth in primary tumor site. Nevertheless, these cells suppressed tumor metastasis in vivo and reduced cancer cell motility in vitro, while Gr1+CD11b+B220- cells from tumor-bearing mice spleens promoted tumor metastasis and enhanced cancer cell motility. Furthermore, both the polymorphonuclear (PMN-MDSCs) and monocytic MDSCs (Mo-MDSCs) could be further divided into B220- and B220+ subsets; interestingly, tumor only induced the expansion of B220- PMN-MDSCs and B220- Mo-MDSCs, but not the B220+ counterparts. Compared with B220- PMN-MDSCs and B220- Mo-MDSCs, the Ly6G+Ly6C-CD11b+B220+ and Ly6G-Ly6C+CD11b+B220+ cells from tumor-bearing mice spleens exhibited a more mature phenotype without immunosuppressive activity. Additionally, IL-6 deficiency attenuated the tumor-induced accumulation of MDSCs, B220- MDSCs and B220- PMN-MDSCs but increased the percentages of Gr1+CD11b+B220+, Ly6G+Ly6C-CD11b+B220+, and Ly6G-Ly6C+CD11b+B220+ cells, indicating the opposing roles of the IL-6 signaling pathway in the expansion of B220- MDSCs and their B220+ counterparts. Taken together, our findings indicate that the B220+ subset is a distinct subset of Gr1+CD11b+ cells functionally different from the B220- subpopulation during tumorigenesis and induction of MDSCs to B220+ cells may be helpful for cancer therapy.
| S-EPMC8057082 | biostudies-literature
Project description:The malignant cells of classical Hodgkin's lymphoma (cHL), Hodgkin and Reed-Sternberg (HRS) cells, appear to be derived from germinal center (GC) B cells in most cases of the disease. Apart from recent findings of constitutive activation of some transcription factors and autocrine stimulation by cytokine receptors, the mechanisms of malignant transformation in cHL still remain poorly understood. We performed a large scale gene expression study using serial analysis of gene expression (SAGE), comparing the cHL cell line L1236 and human GC B cells. Semiquantitative RT-PCR was used to confirm results from the SAGE and to analyze gene expression in 3 additional cHL cell lines. To investigate expression of some genes in cHL cases, we applied RT-PCR on microdissected HRS cells. In total, 464 genes showed a change in expression level of 5-fold or higher. For 12 genes (out of 177) identified as upregulated in L1236 cells, RT-PCR confirmed the SAGE results and also showed elevated expression in 3 other cHL cell lines. For 3 of the upregulated genes, expression by HRS cells in the tissue also was confirmed. Several of the differentially expressed genes may play a role in the pathogenesis of cHL because they represent potential oncogenes, such as rhoC, L-myc, and PTP4A, or transcription factors, such as ATF-5, ATBF1, and p21SNFT. The genes that showed significantly deregulated expression in HRS cells should be helpful not only for the identification of genes involved in the pathogenesis of cHL but also for discovering potential prognostic markers or therapeutic targets.
| S-EPMC1430727 | biostudies-literature