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An ontogenetic switch in the positive and negative selection of B cells

ABSTRACT: An ontogenetic switch in the positive and negative selection of B cells

PROVIDER: PRJNA559543 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9879320_1.fastq.gz	Fastqsanger.gz
	SRR9879320_2.fastq.gz	Fastqsanger.gz
	SRR9879321_1.fastq.gz	Fastqsanger.gz
	SRR9879321_2.fastq.gz	Fastqsanger.gz
	SRR9879322_1.fastq.gz	Fastqsanger.gz

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An ontogenetic switch in the positive and negative selection of B cells [IgHEL]

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An ontogenetic switch in the positive and negative selection of B cells [B cell subsets]

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An ontogenetic switch in the positive and negative selection of B cells [IgHEL]

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.

2020-02-26 | GSE135648 | GEO

An ontogenetic switch in the positive and negative selection of B cells [B cell subsets]

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An ontogenetic switch in the positive and negative selection of B cells [bone marrow and fetal liver]

2020-02-26 | GSE135224 | GEO

An ontogenetic switch in the positive and negative selection of B cells [bone marrow and fetal liver]

Project description:An ontogenetic switch in the positive and negative selection of B cells [bone marrow and fetal liver]

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An ontogenetic switch drives the positive and negative selection of B cells.

Project description:Developing B cells can be positively or negatively selected by self-antigens, but the mechanisms that determine these outcomes are incompletely understood. Here, we show that a B cell intrinsic switch between positive and negative selection during ontogeny is determined by a change from Lin28b to let-7 gene expression. Ectopic expression of a Lin28b transgene in murine B cells restored 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 identified Lin28b-dependent genes associated with B-1 B cell development, including Arid3a and Bhleh41, and Lin28b-independent effects are 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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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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An ontogenetic switch in the positive and negative selection of B cells

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

2020-02-26 | GSE135650 | GEO

Proteasome alteration between epithelial and hematopoietic cells facilitates positive selection of CD8 T cells

Project description:The thymoproteasome, a proteolytic complex uniquely expressed in cortical thymic epithelial cells (cTECs), governs the positive selection of CD8 T cells. It was hypothesized that the thymoproteasome promotes CD8 T cell development by forging a sequential switch between cTECs and medullary antigen-presenting cells (APCs), in which stepwise difference in MHC-I-associated peptides by cTECs and medullary APCs would spare positively selected thymocytes from subsequent negative selection. In this study, we engineered mice ectopically expressing thymoproteasomes in various APCs including medullary TECs (mTECs), eliminating the proposed proteasome switch. Surprisingly, we found that the proteasome switch between cTECs and mTECs was dispensable for thymoproteasome-dependent CD8 T cell development. Instead, we found that ectopic thymoproteasomes in hematopoietic cells impaired CD8 T cell development by hindering cortical positive selection.Our findings reveal that proteasome difference between cTECs and hematopoietic cells facilitates thymoproteasome-dependent positive selection in the thymic cortex.

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