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...

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Autores principales: Rauschmeier, René, Reinhardt, Annika, Gustafsson, Charlotte, Glaros, Vassilis, Artemov, Artem V., Dunst, Josefine, Taneja, Reshma, Adameyko, Igor, Månsson, Robert, Busslinger, Meinrad, Kreslavsky, Taras
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Rockefeller University Press 2021
Materias:
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.
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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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