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| Status |
Public on Feb 26, 2020 |
| Title |
An ontogenetic switch in the positive and negative selection of B cells [IgHEL] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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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| |
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| Overall design |
Examination of the transcriptome from B cells isolated from bone marrow following 10 weeks and 3 weeks from IgHEL transgenic mice
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| |
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| Contributor(s) |
Cribbs AP, Xu X |
| Citation(s) |
32019891 |
| |
| Submission date |
Aug 09, 2019 |
| Last update date |
Feb 26, 2020 |
| Contact name |
Adam Cribbs |
| E-mail(s) |
[email protected]
|
| Organization name |
University of Oxford
|
| Department |
NDORMS
|
| Street address |
Windmill Road
|
| City |
Oxford |
| ZIP/Postal code |
OX37LD |
| Country |
United Kingdom |
| |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
|
| Samples (6)
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| This SubSeries is part of SuperSeries: |
| GSE135650 |
An ontogenetic switch in the positive and negative selection of B cells |
|
| Relations |
| BioProject |
PRJNA559547 |
| SRA |
SRP217960 |
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