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An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling

The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR)...

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Autores principales: Sciammas, Roger, Li, Ying, Warmflash, Aryeh, Song, Yiqiang, Dinner, Aaron R, Singh, Harinder
Formato: Online Artículo Texto
Lenguaje:English
Publicado: European Molecular Biology Organization 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130558/
https://www.ncbi.nlm.nih.gov/pubmed/21613984
http://dx.doi.org/10.1038/msb.2011.25
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author Sciammas, Roger
Li, Ying
Warmflash, Aryeh
Song, Yiqiang
Dinner, Aaron R
Singh, Harinder
author_facet Sciammas, Roger
Li, Ying
Warmflash, Aryeh
Song, Yiqiang
Dinner, Aaron R
Singh, Harinder
author_sort Sciammas, Roger
collection PubMed
description The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of ‘kinetic control’, in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates.
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spelling pubmed-31305582011-07-06 An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling Sciammas, Roger Li, Ying Warmflash, Aryeh Song, Yiqiang Dinner, Aaron R Singh, Harinder Mol Syst Biol Article The B-lymphocyte lineage is a leading system for analyzing gene regulatory networks (GRNs) that orchestrate distinct cell fate transitions. Upon antigen recognition, B cells can diversify their immunoglobulin (Ig) repertoire via somatic hypermutation (SHM) and/or class switch DNA recombination (CSR) before differentiating into antibody-secreting plasma cells. We construct a mathematical model for a GRN underlying this developmental dynamic. The intensity of signaling through the Ig receptor is shown to control the bimodal expression of a pivotal transcription factor, IRF-4, which dictates B cell fate outcomes. Computational modeling coupled with experimental analysis supports a model of ‘kinetic control’, in which B cell developmental trajectories pass through an obligate transient state of variable duration that promotes diversification of the antibody repertoire by SHM/CSR in direct response to antigens. More generally, this network motif could be used to translate a morphogen gradient into developmental inductive events of varying time, thereby enabling the specification of distinct cell fates. European Molecular Biology Organization 2011-05-24 /pmc/articles/PMC3130558/ /pubmed/21613984 http://dx.doi.org/10.1038/msb.2011.25 Text en Copyright © 2011, EMBO and Macmillan Publishers Limited https://creativecommons.org/licenses/by-nc-sa/3.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Noncommercial Share Alike 3.0 Unported License, which allows readers to alter, transform, or build upon the article and then distribute the resulting work under the same or similar license to this one. The work must be attributed back to the original author and commercial use is not permitted without specific permission.
spellingShingle Article
Sciammas, Roger
Li, Ying
Warmflash, Aryeh
Song, Yiqiang
Dinner, Aaron R
Singh, Harinder
An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling
title An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling
title_full An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling
title_fullStr An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling
title_full_unstemmed An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling
title_short An incoherent regulatory network architecture that orchestrates B cell diversification in response to antigen signaling
title_sort incoherent regulatory network architecture that orchestrates b cell diversification in response to antigen signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3130558/
https://www.ncbi.nlm.nih.gov/pubmed/21613984
http://dx.doi.org/10.1038/msb.2011.25
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