Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by dysregulated plasmablast generation and the production of autoantibodies. In Cell Metabolism, Zeng et al. examined metabolic differences between B cells obtained from individuals with SLE and healthy controls. SLE B cells had higher mitochondrial respiratory activity and increased utilization of fatty acid oxidation as compared to cells from healthy controls. Notably, genes (CD36, FABP4 and CPT1A) associated with fatty acid uptake and metabolism were also increased. CD19+IgD−CD27−CD11c+ B cells and CD19+IgD−CD27+CD38+ antibody-secreting cells consistently had the highest uptake of lipids as compared with other B cell subsets. Similar changes were observed in B cells of NZM2328 mice, a mouse model of SLE. In vitro coculture of B cells with splenic fibroblastic reticular cells (FRCs) increased the expression of CD36 and FABP4, as well as lipid uptake and metabolism. Notably, B cell coculture also increased expression of choline acetyltransferase (ChAT) by FRCs. FRCs secrete acetylcholine (ACh), which signals through ACh receptors on B cells to increase lipid utilization via Ca2+-dependent NFAT activation. Injection of wild-type FRCs into NZM2328 mice increased the number of pathogenic antibody-secreting cells that secrete anti-DNA antibodies; however, knockdown of ChAT in FRCs before infusion blunted this response. These findings point to an FRC–B cell axis that enhances B cell activation and plasmablast formation, including potentially pathogenic B cells.
Original reference: Cell Metab. https://doi.org/10.1016/j.cmet.2023.03.010 (2023).
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