Abstract
Aging is the greatest risk factor for developing chronic diseases. Inflamm-aging, the age-related increase in low-grade chronic inflammation, may be a common link in age-related diseases. This review summarizes recent published data on potential cellular and molecular mechanisms of the age-related increase in inflammation, and how these contribute to decreased humoral immune responses in aged mice and humans. Briefly, we cover how aging and related inflammation decrease antibody responses in mice and humans, and how obesity contributes to the mechanisms for aging through increased inflammation. We also report data in the literature showing adipose tissue infiltration with immune cells and how these cells are recruited and contribute to local and systemic inflammation. We show that several types of immune cells infiltrate the adipose tissue and these include macrophages, neutrophils, NK cells, innate lymphoid cells, eosinophils, T cells, B1, and B2 cells. Our main focus is how the adipose tissue affects immune responses, in particular B cell responses and antibody production. The role of leptin in generating inflammation and decreased B cell responses is also discussed. We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies.
Highlights
We report data published by us and by other groups showing that the adipose tissue generates pro-inflammatory B cell subsets which induce pro-inflammatory T cells, promote insulin resistance, and secrete pathogenic autoimmune antibodies
These pro-inflammatory processes amplify each other and have systemic consequences. These results suggest that cellular senescence is a stress-induced adaptive response that develops through major metabolic and secretory readjustments
When we measured the percentages of the major peripheral B cell subsets [follicular (FO), age-associated B cells (ABCs), and marginal zone] in the spleens and epididymal visceral adipose tissue (VAT) of young and old mice, we found reduced percentages of the FO subset in the spleen of old versus young mice and concomitant increased percentages of the pro-inflammatory ABC subset as previously shown [29, 91,92,93]
Summary
Aged mice and humans have a poor immune response against infectious agents and vaccines [1]. Our laboratory has characterized age-related autonomous B cell defects, which are responsible for sub-optimal antibody responses of elderly individuals to infections and vaccines [16,17,18,19,20]. These include a reduction in activation-induced cytidine deaminase (AID), the enzyme necessary for class switch recombination, somatic hypermutation, and IgG production, as well as in E47 [13, 21], a key transcription factor regulating AID [22]. We demonstrated that increased TNF-α either in serum or in B cells contributes to sub-optimal antibody responses and we consider this to be a condition where the B cells have been made “refractory” to further stimulation by chronic stimulation with inflammatory cytokines
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