Influence of nutrients and metabolites on the differentiation of plasma cells and implications for autoimmunity

Abstract

The modulation of inflammatory (auto)immune reactions by nutrients and gut bacterial metabolites is of great interest for potential preventive and therapeutic strategies. B cell-derived plasma cells are major players in inflammatory (auto)immune responses and can exhibit pro- or anti-inflammatory effects through (auto)antibody-dependent and -independent functions. Emerging evidence indicates a key role of nutrients and microbial metabolites in regulating the differentiation of plasma cells as well as their differentiation to pro- or anti-inflammatory phenotypes. These effects might be mediated indirectly by influencing other immune cells or directly through B cell-intrinsic mechanisms. Here, we provide an overview of nutrients and metabolites that influence B cell-intrinsic signaling pathways regulating B cell activation, plasma cell differentiation, and effector functions. Furthermore, we outline important inflammatory plasma cell phenotypes whose differentiation could be targeted by nutrients and microbial metabolites. Finally, we discuss possible implications for inflammatory (auto)immune conditions.

The ICF2 gene Zbtb24 specifically regulates the differentiation of B1 cellsviapromoting heme synthesis

“…Enormous studies recently showed that the activation and function of lymphocytes are intertwined with metabolic reprogramming & adaption (Boothby and Rickert, 2017; Foh et al, 2022; Jellusova, 2018). In association with the altered function, multiple genes relating to nutrients uptake and metabolism, such as Slc2a1/Glut1, Slc16a3/Mct3, Ak4, Pdk1, Pfkl, and Tpi, were significantly upregulated in Zbtb24 B-CKO B1 cells ( Figure S10A ).…”

“…Irf4 regulates both of these processes as intermediate Irf4 induces Bcl6 and activation-induced cytidine deaminase (AID), which initiates SHM & CSR, while its high expression upregulates Prdm1 (Ochiai et al, 2013). In addition to the timely & spatially regulated expressions of these TFs, recent studies showed that metabolic reprogramming/adaptation shapes the differentiation & function of B cells as well (Boothby and Rickert, 2017; Foh et al, 2022; Jellusova, 2018). mTORC1 coordinates the increased anabolism and thus plays an essential role in the activation, proliferation and protein synthesis of cells that demand increased energy and building blocks (Boothby et al, 2022).…”