| First Author | Wilson JJ | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 9 | Pages | 107487 |
| PubMed ID | 37636066 | Mgi Jnum | J:339615 |
| Mgi Id | MGI:7523703 | Doi | 10.1016/j.isci.2023.107487 |
| Citation | Wilson JJ, et al. (2023) Glucose oxidation-dependent survival of activated B cells provides a putative novel therapeutic target for lupus treatment. iScience 26(9):107487 |
| abstractText | Aberrant metabolic demand is observed in immune/inflammatory disorders, yet the role in pathogenesis remains unclear. Here, we discover that in lupus, activated B cells, including germinal center B (GCB) cells, have remarkably high glycolytic requirement for survival over T cell populations, as demonstrated by increased metabolic activity in lupus-activated B cells compared to immunization-induced cells. The augmented reliance on glucose oxidation makes GCB cells vulnerable to mitochondrial ROS-induced oxidative stress and apoptosis. Short-term glycolysis inhibition selectively reduces pathogenic activated B in lupus-prone mice, extending their lifespan, without affecting T follicular helper cells. Particularly, BCMA-expressing GCB cells rely heavily on glucose oxidation. Depleting BCMA-expressing activated B cells with APRIL-based CAR-T cells significantly prolongs the lifespan of mice with severe autoimmune disease. These results reveal that glycolysis-dependent activated B and GCB cells, especially those expressing BCMA, are potentially key lupus mediators, and could be targeted to improve disease outcomes. |
