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The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells

Antibody secretion by plasma cells provides acute and long-term protection against pathogens. The high secretion potential of plasma cells depends on the unfolded protein response, which is controlled by the transcription factor Xbp1. Here, we analyzed the Xbp1-dependent gene expression program of p...

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Autores principales: Wöhner, Miriam, Pinter, Theresa, Bönelt, Peter, Hagelkruys, Astrid, Kostanova-Poliakova, Daniela, Stadlmann, Johannes, Konieczny, Stephen F., Fischer, Maria, Jaritz, Markus, Busslinger, Meinrad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811352/
https://www.ncbi.nlm.nih.gov/pubmed/36618345
http://dx.doi.org/10.3389/fimmu.2022.859598
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author Wöhner, Miriam
Pinter, Theresa
Bönelt, Peter
Hagelkruys, Astrid
Kostanova-Poliakova, Daniela
Stadlmann, Johannes
Konieczny, Stephen F.
Fischer, Maria
Jaritz, Markus
Busslinger, Meinrad
author_facet Wöhner, Miriam
Pinter, Theresa
Bönelt, Peter
Hagelkruys, Astrid
Kostanova-Poliakova, Daniela
Stadlmann, Johannes
Konieczny, Stephen F.
Fischer, Maria
Jaritz, Markus
Busslinger, Meinrad
author_sort Wöhner, Miriam
collection PubMed
description Antibody secretion by plasma cells provides acute and long-term protection against pathogens. The high secretion potential of plasma cells depends on the unfolded protein response, which is controlled by the transcription factor Xbp1. Here, we analyzed the Xbp1-dependent gene expression program of plasma cells and identified Bhlha15 (Mist1) as the most strongly activated Xbp1 target gene. As Mist1 plays an important role in other secretory cell types, we analyzed in detail the phenotype of Mist1-deficient plasma cells in Cd23-Cre Bhlha15 (fl/fl) mice under steady-state condition or upon NP-KLH immunization. Under both conditions, Mist1-deficient plasma cells were 1.4-fold reduced in number and exhibited increased IgM production and antibody secretion compared to control plasma cells. At the molecular level, Mist1 regulated a largely different set of target genes compared with Xbp1. Notably, expression of the Blimp1 protein, which is known to activate immunoglobulin gene expression and to contribute to antibody secretion, was 1.3-fold upregulated in Mist1-deficient plasma cells, which led to a moderate downregulation of most Blimp1-repressed target genes in the absence of Mist1. Importantly, a 2-fold reduction of Blimp1 (Prdm1) expression was sufficient to restore the cell number and antibody expression of plasma cells in Prdm1 (Gfp/+) Cd23-Cre Bhlha15 (fl/fl) mice to the same level seen in control mice. Together, these data indicate that Mist1 restricts antibody secretion by restraining Blimp1 expression, which likely contributes to the viability of plasma cells.
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spelling pubmed-98113522023-01-05 The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells Wöhner, Miriam Pinter, Theresa Bönelt, Peter Hagelkruys, Astrid Kostanova-Poliakova, Daniela Stadlmann, Johannes Konieczny, Stephen F. Fischer, Maria Jaritz, Markus Busslinger, Meinrad Front Immunol Immunology Antibody secretion by plasma cells provides acute and long-term protection against pathogens. The high secretion potential of plasma cells depends on the unfolded protein response, which is controlled by the transcription factor Xbp1. Here, we analyzed the Xbp1-dependent gene expression program of plasma cells and identified Bhlha15 (Mist1) as the most strongly activated Xbp1 target gene. As Mist1 plays an important role in other secretory cell types, we analyzed in detail the phenotype of Mist1-deficient plasma cells in Cd23-Cre Bhlha15 (fl/fl) mice under steady-state condition or upon NP-KLH immunization. Under both conditions, Mist1-deficient plasma cells were 1.4-fold reduced in number and exhibited increased IgM production and antibody secretion compared to control plasma cells. At the molecular level, Mist1 regulated a largely different set of target genes compared with Xbp1. Notably, expression of the Blimp1 protein, which is known to activate immunoglobulin gene expression and to contribute to antibody secretion, was 1.3-fold upregulated in Mist1-deficient plasma cells, which led to a moderate downregulation of most Blimp1-repressed target genes in the absence of Mist1. Importantly, a 2-fold reduction of Blimp1 (Prdm1) expression was sufficient to restore the cell number and antibody expression of plasma cells in Prdm1 (Gfp/+) Cd23-Cre Bhlha15 (fl/fl) mice to the same level seen in control mice. Together, these data indicate that Mist1 restricts antibody secretion by restraining Blimp1 expression, which likely contributes to the viability of plasma cells. Frontiers Media S.A. 2022-12-21 /pmc/articles/PMC9811352/ /pubmed/36618345 http://dx.doi.org/10.3389/fimmu.2022.859598 Text en Copyright © 2022 Wöhner, Pinter, Bönelt, Hagelkruys, Kostanova-Poliakova, Stadlmann, Konieczny, Fischer, Jaritz and Busslinger https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wöhner, Miriam
Pinter, Theresa
Bönelt, Peter
Hagelkruys, Astrid
Kostanova-Poliakova, Daniela
Stadlmann, Johannes
Konieczny, Stephen F.
Fischer, Maria
Jaritz, Markus
Busslinger, Meinrad
The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells
title The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells
title_full The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells
title_fullStr The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells
title_full_unstemmed The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells
title_short The Xbp1-regulated transcription factor Mist1 restricts antibody secretion by restraining Blimp1 expression in plasma cells
title_sort xbp1-regulated transcription factor mist1 restricts antibody secretion by restraining blimp1 expression in plasma cells
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9811352/
https://www.ncbi.nlm.nih.gov/pubmed/36618345
http://dx.doi.org/10.3389/fimmu.2022.859598
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