Conditional Bhlhe40 inactivation confirmed cell-autonomous functions of Bhlhe40 in both GC B and TFH cells, while the GC phenotype was further enhanced upon loss of Bhlhe40 in both cell types. 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.
In activated CD4 T cells, Bhlhe40 was required to restrain proliferation thus limiting the number of TFH cells. 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. Intriguingly, several key positive regulators of the GC reaction are common for both cell types. The generation of high-affinity antibodies against pathogens and vaccines requires the germinal center (GC) reaction – a process that relies on a complex interplay between specialized effector subsets of B and CD4 T lymphocytes – GC B cells and T follicular helper (TFH) cells. GEO help: Mouse over screen elements for information.Ĭell‐intrinsic functions of Bhlhe40 in activated B cells and TFH cells restrain the GC reaction and prevent lymphomagenesisĮxpression profiling by high throughput sequencing
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