StressCovidV1, Main, Exploration, bibRecord, 000873

Metabolic requirements of human pro-inflammatory B cells in aging and obesity.

Identifieur interne : 000873 ( Main/Exploration ); précédent : 000872; suivant : 000874

Metabolic requirements of human pro-inflammatory B cells in aging and obesity.

Auteurs : Daniela Frasca [États-Unis] ; Alain Diaz [États-Unis] ; Maria Romero [États-Unis] ; Seth Thaller [États-Unis] ; Bonnie B. Blomberg [États-Unis]

Source :

PloS one [ 1932-6203 ] ; 2019.

RBID : pubmed:31287846

Descripteurs français

English descriptors

KwdEn :
- AMP-Activated Protein Kinases (metabolism), Adult, Aged, Aging (genetics), Aging (metabolism), Autoimmunity, B-Lymphocyte Subsets (metabolism), Biomarkers, Energy Metabolism (genetics), Gene Expression Regulation, Humans, Middle Aged, Obesity (genetics), Obesity (metabolism), Oxidative Stress, RNA, Messenger, Reactive Oxygen Species, T-Box Domain Proteins (genetics), T-Box Domain Proteins (metabolism), Young Adult.
MESH :
- chemical , genetics : T-Box Domain Proteins.
- chemical , metabolism : AMP-Activated Protein Kinases, T-Box Domain Proteins.
- genetics : Aging, Energy Metabolism, Obesity.
- metabolism : Aging, B-Lymphocyte Subsets, Obesity.
- Adult, Aged, Autoimmunity, Biomarkers, Gene Expression Regulation, Humans, Middle Aged, Oxidative Stress, RNA, Messenger, Reactive Oxygen Species, Young Adult.

Abstract

The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. 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. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5'-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies).

DOI: 10.1371/journal.pone.0219545
PubMed: 31287846

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en">The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. 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. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5'-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies).</div>
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Metabolic requirements of human pro-inflammatory B cells in aging and obesity.

Metabolic requirements of human pro-inflammatory B cells in aging and obesity.

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Descripteurs français

English descriptors

Abstract

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