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Title: Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.
Authors: Rauschmeier, René
Reinhardt, Annika
Gustafsson, Charlotte
Glaros, Vassilis
Artemov, Artem V
Dunst, Josefine
Taneja, Reshma 
Adameyko, Igor
Månsson, Robert
Busslinger, Meinrad
Kreslavsky, Taras
Issue Date: 7-Feb-2022
Publisher: Rockefeller University Press
Citation: Rauschmeier, René, Reinhardt, Annika, Gustafsson, Charlotte, Glaros, Vassilis, Artemov, Artem V, Dunst, Josefine, Taneja, Reshma, Adameyko, Igor, Månsson, Robert, Busslinger, Meinrad, Kreslavsky, Taras (2022-02-07). Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis.. J Exp Med 219 (2). ScholarBank@NUS Repository.
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.
Source Title: J Exp Med
ISSN: 00221007
DOI: 10.1084/jem.20211406
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