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).
Highlights
Aging is associated with poor B cell function and decreased production of protective antibodies and we have shown that both systemic and B cell intrinsic inflammation contribute to this [1,2,3]
We found that only memory B cells express senescence-associated secretory phenotype (SASP) markers, and especially the CD19+IgD-CD27- B cell subset, called late memory (LM), tissuelike or double negative (DN), which is the most pro-inflammatory B cell subset, as compared to IgM memory and switched memory B cells [15]
Results presented show that DN B cells accumulate in the blood of elderly individuals, do not proliferate to stimuli and do not make antibodies to influenza antigens
Summary
Aging is associated with poor B cell function and decreased production of protective antibodies and we have shown that both systemic and B cell intrinsic inflammation contribute to this [1,2,3]. We found that only memory B cells express SASP markers, and especially the CD19+IgD-CD27- B cell subset, called late memory (LM), tissuelike or double negative (DN), which is the most pro-inflammatory B cell subset, as compared to IgM memory and switched memory B cells [15] This subset, that we previously called LM [15] and DN in agreement with the other groups, has been reported to be increased in the blood of healthy elderly individuals [15, 16], and in patients with autoimmune [17,18,19,20,21,22] and infectious diseases [23,24,25]. The role of metabolic changes in driving the secretion of pathogenic (autoimmune) antibodies is unknown
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
