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Repression of the B cell identity factor Pax5 is not required for plasma cell development

B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential f...

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Autores principales: Liu, Grace J., Jaritz, Markus, Wöhner, Miriam, Agerer, Benedikt, Bergthaler, Andreas, Malin, Stephen G., Busslinger, Meinrad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596824/
https://www.ncbi.nlm.nih.gov/pubmed/32780801
http://dx.doi.org/10.1084/jem.20200147
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author Liu, Grace J.
Jaritz, Markus
Wöhner, Miriam
Agerer, Benedikt
Bergthaler, Andreas
Malin, Stephen G.
Busslinger, Meinrad
author_facet Liu, Grace J.
Jaritz, Markus
Wöhner, Miriam
Agerer, Benedikt
Bergthaler, Andreas
Malin, Stephen G.
Busslinger, Meinrad
author_sort Liu, Grace J.
collection PubMed
description B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the Igh(Pax5/+) mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young Igh(Pax5/+) mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in Igh(Pax5/+) plasma cells. While IgM and IgA secretion by Igh(Pax5/+) plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells.
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spelling pubmed-75968242021-05-02 Repression of the B cell identity factor Pax5 is not required for plasma cell development Liu, Grace J. Jaritz, Markus Wöhner, Miriam Agerer, Benedikt Bergthaler, Andreas Malin, Stephen G. Busslinger, Meinrad J Exp Med Article B cell and plasma cell fates are controlled by different transcriptional networks, as exemplified by the mutually exclusive expression and cross-antagonism of the B cell identity factor Pax5 and the plasma cell regulator Blimp1. It has been postulated that repression of Pax5 by Blimp1 is essential for plasma cell development. Here, we challenged this hypothesis by analyzing the Igh(Pax5/+) mouse, which expressed a Pax5 minigene from the immunoglobulin heavy-chain locus. Despite high Pax5 expression, plasma cells efficiently developed in young Igh(Pax5/+) mice at steady state and upon immunization, while their number moderately declined in older mice. Although Pax5 significantly deregulated the plasma cell expression program, key plasma cell regulators were normally expressed in Igh(Pax5/+) plasma cells. While IgM and IgA secretion by Igh(Pax5/+) plasma cells was normal, IgG secretion was modestly decreased. Hence, Pax5 repression is not essential for robust plasma cell development and antibody secretion, although it is required for optimal IgG production and accumulation of long-lived plasma cells. Rockefeller University Press 2020-08-11 /pmc/articles/PMC7596824/ /pubmed/32780801 http://dx.doi.org/10.1084/jem.20200147 Text en © 2020 Liu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Liu, Grace J.
Jaritz, Markus
Wöhner, Miriam
Agerer, Benedikt
Bergthaler, Andreas
Malin, Stephen G.
Busslinger, Meinrad
Repression of the B cell identity factor Pax5 is not required for plasma cell development
title Repression of the B cell identity factor Pax5 is not required for plasma cell development
title_full Repression of the B cell identity factor Pax5 is not required for plasma cell development
title_fullStr Repression of the B cell identity factor Pax5 is not required for plasma cell development
title_full_unstemmed Repression of the B cell identity factor Pax5 is not required for plasma cell development
title_short Repression of the B cell identity factor Pax5 is not required for plasma cell development
title_sort repression of the b cell identity factor pax5 is not required for plasma cell development
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7596824/
https://www.ncbi.nlm.nih.gov/pubmed/32780801
http://dx.doi.org/10.1084/jem.20200147
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