Obesity Accelerates Age Defects in Mouse and Human B Cells

Abstract

Obesity, similar to aging, is associated with chronic low-grade systemic inflammation, known as inflammaging, and represents a significantly higher risk for developing chronic diseases typical of old age. Immune cells are recruited to the obese adipose tissue (AT) by chemotactic molecules secreted by non-immune and immune cells in the AT, both contributing to the release of several pro-inflammatory mediators that fuel local and systemic inflammation, to the refractory response of immune cells to further in vivo and in vitro stimulation and to the induction of autoimmune B cells with potentially pathogenic repertoires. In terms of molecular mechanisms involved, leptin, an adipokine secreted primarily by adipocytes, has been proposed to be involved in the reduced generation of protective antibodies, and in the increased generation of autoimmune antibodies, further supporting the concept that obesity accelerates age defects. Leptin has also been shown to induce intrinsic B cell inflammation and B cell immunosenescence. The results presented in this review highlight the importance of weight reduction programs to improve immunity and reduce the risk for developing chronic diseases in obese and older individuals.

COVID-19 mRNA vaccine protects against SARS-CoV-2 Omicron BA.1 infection in diet-induced obese mice through boosting host innate antiviral responses

“…These findings indicate that the adaptive B cell responses to mRNA vaccine are severely weakened in DIO mice, which may be due to impairments in B cell development, activation, and functions. 64 , 65 , 66 Interestingly, vaccination offered a certain degree of protection to Omicron BA.1-challenged DIO mice in the lower respiratory but not in the nasal turbinates of infected animals. The insufficient protection in the nasal turbinate tissues may be due to insufficient mucosal immune responses upon intra-muscular vaccination that failed to evoke sufficient protective immunity at the mucosal sites.…”

T and B Cell Composition and Cytokine Producing Capacity Before and After Bariatric Surgery

“…This pro-inflammatory environment may lead to a shift in immune cell composition and immune function in morbidly obese patients as compared to lean individuals ( 8 , 9 ). Morbid obesity has been shown to decrease B cell function in humans, impairs B cell responses to infections and vaccines ( 10 , 11 ) and leads to loss of T cell regulatory mechanisms ( 12 ). Also, presence of epithelial signals regulating the adipose tissue immunity may be altered in morbidly obese individuals ( 13 ).…”

Immune cell profile and immune‐related gene expression of obese peripheral blood and liver tissue

“…A previous study in obese individuals found elevated B cell activity with a shift in activated subsets associated with an increase in antigen-producing plasmablasts and a reduction in resting memory B cells [51]. Interestingly, Blomberg et al have also demonstrated that the B cell population in obese individuals are enriched with a pro-inflammatory subset of memory B cells comparable to those of old age or with autoimmune conditions [52,53]. To add further complexity, B cells are also critical regulators of T cellmediated inflammation and a reduction in Treg that is associated with obesity and type 2 diabetes [54,55].…”