Centre for Biological Signalling Studies

The role of metabolic checkpoint regulators in B cell survival and transformation

Jellusova J.

Immunol Rev. 2020;295(1):39-53

Immunol Rev.              online article

In response to mitogenic stimulation, B cells activate different pro-anabolic signaling pathways such as c-Myc- and mTORC1-dependent networks to satisfy the energetic demands of biomass synthesis and proliferation. In order to preserve viability and function, cell growth cannot progress unchecked and must be adjusted according to the availability of nutrients. Nutrient-sensing proteins such as AMPK antagonize mTORC1 activity in response to starvation. If pro-anabolic signaling pathways are aberrantly activated, B cells may lack the metabolic capacity to accommodate their energetic needs, which can lead to cell death. On the other hand, metabolic hyperactivation is a salient feature of cancer cells, suggesting that mechanisms exist, which allow B cells to cope with metabolic stress. The aim of this review is to discuss how B cells respond to a mismatch between energy supply and demand and what the consequences are of metabolic dysregulation in normal and malignant B cells.