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Lin28b augments protein synthesis to control B cell positive selection early in life.

ABSTRACT: Lin28b augments protein synthesis to control B cell positive selection early in life.

PROVIDER: PRJNA900541 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22262365_1.fastq.gz	Fastqsanger.gz
	SRR22262365_2.fastq.gz	Fastqsanger.gz
	SRR22262366_1.fastq.gz	Fastqsanger.gz
	SRR22262366_2.fastq.gz	Fastqsanger.gz
	SRR22262367_1.fastq.gz	Fastqsanger.gz

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Lin28b augments protein synthesis to control B cell positive selection early in life [RIP-seq]

Project description:Lin28b augments protein synthesis to control B cell positive selection early in life [RIP-seq]

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Lin28b augments protein synthesis to control B cell positive selection early in life [RNA-seq]

Project description:Lin28b augments protein synthesis to control B cell positive selection early in life [RNA-seq]

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Lin28b augments protein synthesis to control B cell positive selection early in life [RIP-seq]

Project description:In this study, we identify elevated protein synthesis as a defining characteristic of early life B cell development and a determinant for the qualitative switch in B cell output whereby self-reactive CD5+ B-1 cells becomes censored in postnatal mice This is in part mediated by the heterochronic RNA binding protein LIN28B. To identify Lin28b-dependent, stage specific effects, B cell progenitors at different developmental stages were sorted and analyzed by RNA-seq

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Lin28b augments protein synthesis to control B cell positive selection early in life.

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

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Lin28b controls a neonatal to adult switch in B cell positive selection

Project description:The ability of B-1 cells to become positively selected into the mature B cell pool, despite being weakly self-reactive, has puzzled the field since its initial discovery. Here, we explore changes in B cell positive selection as a function of developmental time by exploiting a link between CD5 surface levels and the natural occurrence of self-reactive B cell receptors (BCRs) in BCR wildtype mice. We show that the heterochronic RNA-binding protein Lin28b potentiates a neonatal mode of B cell selection characterized by enhanced overall positive selection and the developmental progression of CD5+ immature B cells in particular. Importantly, Lin28b achieves this through amplifying the CD19/PI3K/c-Myc positive feedback loop and ectopic Lin28b expression restores both positive selection and mature B cell numbers in CD19–/– adult mice. Thus, the temporally restricted expression of Lin28b alters the rules for B cell selection during ontogeny through modulating tonic signaling. We propose that this neonatal mode of B cell selection represents a cell intrinsic cue to accelerate the de novo establishment of the adaptive immune system and incorporate a layer of natural antibody mediated immunity throughout life.

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Lin28b controls a neonatal to adult switch in B cell positive selection

Project description:Lin28b controls a neonatal to adult switch in B cell positive selection

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Project description:Developing B cells can differentiate into a variety of different subsets, but the mechanisms that determine these outcomes are incompletely understood, with theories based on separate lineages or the positive and negative selection by self-antigens. In particular, the development of the B-1 B cell subset arises mainly from precursors in early ontogeny and is subject to positive selection by self-antigens, whereas the follicular B-2 B cell subset arises later and is subject to negative control. In this study we show how a cell intrinsic switch from Lin28b to Let7 gene expression changes a B cell’s susceptibility from positive to negative selection during ontogeny. Ectopic expression of a Lin28b transgene in B cells restores the positive selection of autoreactive B-1 B cells by self-antigen in adult bone marrow. Analysis of antigen-specific immature B cells in early and late ontogeny identifies Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects associated with the presence or absence of self-antigen. These findings identify cell intrinsic and extrinsic determinants of B cell fate during ontogeny and reconcile lineage and selection theories of B cell development. They explain how changes in the balance of positive and negative selection may be able to adapt to meet the immunological needs of an individual during its lifetime.

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