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

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.

In:The Journal of experimental medicine: Rockefeller University Press219:21540-95380022-1007

By the author/editor: Rauschmeier, R; Reinhardt, A; Gustafsson, C; Glaros, V; Artemov, AV; Dunst, J; show more...; Taneja, R; Adameyko, I; Mansson, R; Busslinger, M; Kreslavsky, T; show less...

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