Metabolic requirements of human pro-inflammatory B cells in aging and obesity.
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,...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0219545 |
| _version_ | 1797306788664573952 |
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| author | Daniela Frasca Alain Diaz Maria Romero Seth Thaller Bonnie B Blomberg |
| author_facet | Daniela Frasca Alain Diaz Maria Romero Seth Thaller Bonnie B Blomberg |
| author_sort | Daniela Frasca |
| collection | DOAJ |
| description | 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). |
| first_indexed | 2024-03-08T00:46:53Z |
| format | Article |
| id | doaj.art-3e2ee6c197ad4ccead25b3b75ed9b7ae |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-08T00:46:53Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-3e2ee6c197ad4ccead25b3b75ed9b7ae2024-02-15T05:33:03ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e021954510.1371/journal.pone.0219545Metabolic requirements of human pro-inflammatory B cells in aging and obesity.Daniela FrascaAlain DiazMaria RomeroSeth ThallerBonnie B BlombergThe 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).https://doi.org/10.1371/journal.pone.0219545 |
| spellingShingle | Daniela Frasca Alain Diaz Maria Romero Seth Thaller Bonnie B Blomberg Metabolic requirements of human pro-inflammatory B cells in aging and obesity. PLoS ONE |
| title | Metabolic requirements of human pro-inflammatory B cells in aging and obesity. |
| title_full | Metabolic requirements of human pro-inflammatory B cells in aging and obesity. |
| title_fullStr | Metabolic requirements of human pro-inflammatory B cells in aging and obesity. |
| title_full_unstemmed | Metabolic requirements of human pro-inflammatory B cells in aging and obesity. |
| title_short | Metabolic requirements of human pro-inflammatory B cells in aging and obesity. |
| title_sort | metabolic requirements of human pro inflammatory b cells in aging and obesity |
| url | https://doi.org/10.1371/journal.pone.0219545 |
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