Induction of metabolic quiescence defines the transitional to follicular B cell switch.

Induction of metabolic quiescence defines the transitional to follicular B cell switch. Sci Signal. 2019 Oct 22;12(604): Authors: Farmer JR, Allard-Chamard H, Sun N, Ahmad M, Bertocchi A, Mahajan VS, Aicher T, Arnold J, Benson MD, Morningstar J, Barmettler S, Yuen G, Murphy SJH, Walter JE, Ghebremichael M, Shalek AK, Batista F, Gerszten R, Pillai S Abstract Transitional B cells must actively undergo selection for self-tolerance before maturing into their resting follicular B cell successors. We found that metabolic quiescence was acquired at the follicular B cell stage in both humans and mice. In follicular B cells, the expression of genes involved in ribosome biogenesis, aerobic respiration, and mammalian target of rapamycin complex 1 (mTORC1) signaling was reduced when compared to that in transitional B cells. Functional metabolism studies, profiling of whole-cell metabolites, and analysis of cell surface proteins in human B cells suggested that this transition was also associated with increased extracellular adenosine salvage. Follicular B cells increased the abundance of the cell surface ectonucleotidase CD73, which coincided with adenosine 5'-monophosphate-activated protein kinase (AMPK) activation. Differentiation to the follicular B cell stage in vitro correlated with surface acquisition of CD73 on human transitional B cells and was augmented with the AMPK agonist, AICAR. Last, individuals with gain-of-function PIK3CD (PI3Kδ)...
Source: Science Signaling - Category: Biomedical Science Authors: Tags: Sci Signal Source Type: research