De novo pyrimidine synthesis controls germinal center B cell and plasma cell fates and systemic autoimmunity - PubMed
4 hours ago
- #pyrimidine synthesis
- #autoimmunity
- #B cell metabolism
- Enhanced de novo pyrimidine synthesis is observed in B cells prone to systemic lupus erythematosus (SLE).
- Temporal inhibition of pyrimidine synthesis reduces SLE-related germinal center (GC) and plasma cell (PC) responses, but not foreign antigen-specific ones.
- Conditional deletion of uridine monophosphate synthase (UMPS) shows B cell-intrinsic need for de novo pyrimidine synthesis in both foreign and SLE-driven immune responses and kidney deposits.
- Pyrimidine synthesis promotes aerobic glycolysis and oxidative phosphorylation in SLE-prone B cells, supporting a heightened metabolic state and cMYC expression.
- Mechanistically, mTORC1 and S6K1 activated by TLR7 and CD40 signaling enhance pyrimidine synthesis by activating the enzyme CAD.