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, Månsson 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.

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PubMed 34919144

DOI 10.1084/jem.20211406

Crossref 10.1084/jem.20211406

pii: 212923
pmc: PMC8689665