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Bonnie Blomberg, Alain Diaz, Maria Romero, Daniela Frasca, Metabolic reprogramming of human pro-inflammatory B cells in aging and obesity, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 121.8, https://doi.org/10.4049/jimmunol.202.Supp.121.8
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Abstract
The subset of pro-inflammatory B cells, called late memory (LM), tissuelike or double negative (CD19+CD27-IgD-), accumulates in the blood of elderly individuals. Here we show that LM B cells do not proliferate and do not make antibodies to new antigens (influenza vaccine), but they spontaneously secrete antibodies with autoimmune reactivity, due to spontaneous expression of the T-bet transcription factor. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. Here we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and subcutaneous adipose tissue (SAT) of individuals with obesity. Results show a metabolic reprogramming of LM B cells in aging and obesity, with LM B cells from young individuals having minimal metabolic requirements, LM B cells from elderly and obese individuals use higher amounts of glucose, make autoimmune antibodies and have higher aerobic glycolysis to support their function. LM B cells from the SAT have the highest metabolic requirements as they have increased oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. This metabolic reprogramming of LM B cells occurs after activation of AMPK (5′-AMP activated kinase) and Sestrins, both able to mitigate stress and cell death. These results indicate that metabolic reprogramming maintains LM B cells alive and maintains their function (secretion of autoimmune antibodies).
