Glycolysis generates ATP for cellular energy, whereas shunting glucose into the pentose-phosphate pathway (PPP) is needed to generate the antioxidant NADPH that is necessary for cellular redox balance. In Cell, Müschen and colleagues report that B cells, but not myeloid cells, critically require the phosphatase PP2A to maintain their redox balance and viability by redirecting glucose into the PPP. Loss of PP2A increases that oxidative stress of B lineage cells and, notably, B cell–derived leukemias. B cells normally have low expression of PPP enzymes due to repression of G6pdx and G6pd2 by the transcription factors Pax5 and Ikaros, which makes B cells more sensitive to the activity of PP2A. Patient-derived B cell leukemias and lymphomas also show dependence on the activity of PP2A, which suggests that it might be targeted for therapeutic intervention.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dempsey, L.A. PP2A in B cells. Nat Immunol 19, 510 (2018). https://doi.org/10.1038/s41590-018-0098-y
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41590-018-0098-y