Phosphoglycerate dehydrogenase (PHGDH) is the first enzyme in the cascade leading to serine synthesis from glucose within the cell. This study from D'Avola and colleagues examined PHGDH and other serine synthesis components within the germinal center, a structure where B cells are activated to drive antibody-based responses to infection and to generate immune memory. Following discovery via scRNA-seq, the authors used flow cytometry, immunostaining, and labeled carbon assays to demonstrate that high expression and activity of these enzymes is specific to cycling (i.e., activated) B cells. Knockout or inhibition of PHGDH in human cells and mouse models results in impaired antibody production and immune response, as well as induction of apoptosis in lymphomas derived from this compartment.

Expert Commentary: The finding that PHGDH inhibition is apoptosis-inducing in lymphoma cells, but only cytostatic in normal B cells suggests that such inhibition could enable lymphoma treatment while preserving some of the host...

You do not currently have access to this content.