Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis
The generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction, which relies on a complex interplay between specialized effector B and CD4 T lymphocytes, the GC B cells and T follicular helper (T(FH)) cells. Intriguingly, several positive key reg...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689665/ https://www.ncbi.nlm.nih.gov/pubmed/34919144 http://dx.doi.org/10.1084/jem.20211406 |
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author | Rauschmeier, René Reinhardt, Annika Gustafsson, Charlotte Glaros, Vassilis Artemov, Artem V. Dunst, Josefine Taneja, Reshma Adameyko, Igor Månsson, Robert Busslinger, Meinrad Kreslavsky, Taras |
author_facet | Rauschmeier, René Reinhardt, Annika Gustafsson, Charlotte Glaros, Vassilis Artemov, Artem V. Dunst, Josefine Taneja, Reshma Adameyko, Igor Månsson, Robert Busslinger, Meinrad Kreslavsky, Taras |
author_sort | Rauschmeier, René |
collection | PubMed |
description | The generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction, which relies on a complex interplay between specialized effector B and CD4 T lymphocytes, the GC B cells and T follicular helper (T(FH)) cells. Intriguingly, several positive key regulators of the GC reaction are common for both cell types. Here, we report that the transcription factor Bhlhe40 is a crucial cell-intrinsic negative regulator affecting both the B and T cell sides of the GC reaction. In activated CD4 T cells, Bhlhe40 was required to restrain proliferation, thus limiting the number of T(FH) cells. In B cells, Bhlhe40 executed its function in the first days after immunization by selectively restricting the generation of the earliest GC B cells but not of early memory B cells or plasmablasts. Bhlhe40-deficient mice with progressing age succumbed to a B cell lymphoma characterized by the accumulation of monoclonal GC B-like cells and polyclonal T(FH) cells in various tissues. |
format | Online Article Text |
id | pubmed-8689665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-86896652022-07-14 Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis Rauschmeier, René Reinhardt, Annika Gustafsson, Charlotte Glaros, Vassilis Artemov, Artem V. Dunst, Josefine Taneja, Reshma Adameyko, Igor Månsson, Robert Busslinger, Meinrad Kreslavsky, Taras J Exp Med Article The generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction, which relies on a complex interplay between specialized effector B and CD4 T lymphocytes, the GC B cells and T follicular helper (T(FH)) cells. Intriguingly, several positive key regulators of the GC reaction are common for both cell types. Here, we report that the transcription factor Bhlhe40 is a crucial cell-intrinsic negative regulator affecting both the B and T cell sides of the GC reaction. In activated CD4 T cells, Bhlhe40 was required to restrain proliferation, thus limiting the number of T(FH) cells. In B cells, Bhlhe40 executed its function in the first days after immunization by selectively restricting the generation of the earliest GC B cells but not of early memory B cells or plasmablasts. Bhlhe40-deficient mice with progressing age succumbed to a B cell lymphoma characterized by the accumulation of monoclonal GC B-like cells and polyclonal T(FH) cells in various tissues. Rockefeller University Press 2021-12-17 /pmc/articles/PMC8689665/ /pubmed/34919144 http://dx.doi.org/10.1084/jem.20211406 Text en © 2021 Rauschmeier et al. https://creativecommons.org/licenses/by-nc-sa/4.0/http://www.rupress.org/terms/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 Rauschmeier, René Reinhardt, Annika Gustafsson, Charlotte Glaros, Vassilis Artemov, Artem V. Dunst, Josefine Taneja, Reshma Adameyko, Igor Månsson, Robert Busslinger, Meinrad Kreslavsky, Taras Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis |
title | Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis |
title_full | Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis |
title_fullStr | Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis |
title_full_unstemmed | Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis |
title_short | Bhlhe40 function in activated B and T(FH) cells restrains the GC reaction and prevents lymphomagenesis |
title_sort | bhlhe40 function in activated b and t(fh) cells restrains the gc reaction and prevents lymphomagenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8689665/ https://www.ncbi.nlm.nih.gov/pubmed/34919144 http://dx.doi.org/10.1084/jem.20211406 |
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