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Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.

Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.

Authors :
Rauschmeier R
Reinhardt A
Gustafsson C
Glaros V
Artemov AV
Dunst J
Taneja R
Adameyko I
Månsson R
Busslinger M
Kreslavsky T
Source :
The Journal of experimental medicine [J Exp Med] 2022 Feb 07; Vol. 219 (2). Date of Electronic Publication: 2021 Dec 17.
Publication Year :
2022

Abstract

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 (TFH) 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 TFH 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 TFH cells in various tissues.<br />Competing Interests: Disclosures: The authors declare no competing interests exist.<br /> (© 2021 Rauschmeier et al.)

Details

Language :
English
ISSN :
1540-9538
Volume :
219
Issue :
2
Database :
MEDLINE
Journal :
The Journal of experimental medicine
Publication Type :
Academic Journal
Accession number :
34919144
Full Text :
https://doi.org/10.1084/jem.20211406