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.
Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis
Disclosures: The authors declare no competing interests exist.
- Award Id(s): 2017-01118,2018-05973
- Award Id(s): CAN 2018/710
- Award Id(s): M18-0094
- Award Id(s): P28841
- Award Id(s): DU 1964/1-1,RE 4264/1-1
- Award Id(s): 740349-PlasmaCellControl
- Award Id(s): 075-15-2020-784
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René Rauschmeier, Annika Reinhardt, Charlotte Gustafsson, Vassilis Glaros, Artem V. Artemov, Josefine Dunst, Reshma Taneja, Igor Adameyko, Robert Månsson, Meinrad Busslinger, Taras Kreslavsky; Bhlhe40 function in activated B and TFH cells restrains the GC reaction and prevents lymphomagenesis. J Exp Med 7 February 2022; 219 (2): e20211406. doi: https://doi.org/10.1084/jem.20211406
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