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MTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [1]

ABSTRACT: mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [1]

PROVIDER: PRJNA612434 | ENA |

REPOSITORIES: ENA

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mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [2]

Project description:A still unanswered question is what drives the small fraction of activated germinal center (GC) B cells that survive to become long-lived quiescent memory B cells. We found here that a small population of light zone GC cells (CD38intBcl6hi/intEfnb1+) with lower mTORC1 activity favored the memory B cell fate. Constitutively high mTORC1 activity led to defects in formation of the CD38intBcl6hi/intEfnb1+ cells; conversely, decreasing mTORC1 activity resulted in relative enrichment of this memory-prone GC population over the recycling-prone one. Furthermore, the CD38intBcl6hi/intEfnb1+ cells had higher levels of Bcl2 and surface BCR, which in turn, contributed to their survival. Given the positive correlation between the strength of T cell help and mTORC1 activity, our data suggest a model in which weak help from T cells together with provision of an increased survival signal are key for GC B cells to assume a memory B cell fate.

2020-09-13 | GSE147095 | GEO

mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [1]

2020-09-13 | GSE146922 | GEO

mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center

Project description:mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center

| PRJNA613043 | ENA

mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [2]

Project description:mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center [2]

| PRJNA613156 | ENA

mTORC1 and B cell survival signal regulate formation of memory precursors in the germinal center

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-09-13 | GSE147096 | GEO

Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation.

Project description:Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation.

| PRJNA483499 | ENA

Proteome profiling of mouse germinal center B cells

Project description:Productive B cell responses are critical to protect a host from infection. The spleen and lymph nodes are populated by resting follicular B cells, which can enter germinal centers upon antigen encounter. Once in the germinal center, B cells migrate between the dark and light zones, where they undergo somatic hypermutation and selection, respectively. While germinal center B cells have been studied, an intense molecular understanding of these cells/subsets (and the differences between them) is lacking.

2020-04-06 | PXD015524 | Pride

Gene expression profiling in RagC S74C germinal center B cells

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

Activated CARD11 accelerates germinal center kinetics, promoting mTORC1 and terminal differentiation.

Project description:This scRNA-seq experiment is an integral part of a manuscript with the above title. Our analysis of the scRNA-seq data suggests that activated CARD11 promotes immunoglobulin class-switching in germinal center B cells and generation of IgG1-secreting plasma cells.

2018-07-31 | GSE117895 | GEO

ChIPseq analyses in germinal center B cells

Project description:Germinal center B cells were isolated from human tonsil tissue and crosslinked. ChIP was performed on two distinct pools of germinal center cells, each obtained from 3-5 donors. The experiment includes two biological replicates (germinal center cell pools from different donors). ChIP was performed on both pools and subject to library preparation and sequencing. Input DNA was sequenced for both pools.

2015-12-04 | E-GEOD-68349 | biostudies-arrayexpress

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