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

Rauschmeier R, Reinhardt A, Gustafsson C, Glaros V, Artemov AV, Dunst J, Taneja R, Adameyko I, MÃ¥nsson R, Busslinger M, Kreslavsky T

J. Exp. Med. 219 (2) - [2022-02-07; online 2021-12-17]

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.

Bioinformatics Support for Computational Resources [Service]

PubMed 34919144

DOI 10.1084/jem.20211406

Crossref 10.1084/jem.20211406

pii: 212923
pmc: PMC8689665

Publications 9.5.0