GSE125393 Gene expression profiling in RagC S74C germinal center B cells

Contributors : Ana Ortega-Molina ; Kevin Troul é ; Osvaldo Graña ; Alejo EfeyanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusGene expression by RNAseq in murine germinal center B cells induced by SRBC in RagC S74C miceFollicular 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 h...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research