The obesity-induced expression of T-bet in B cells promotes metabolic dysfunction and alters antibody responses

Abstract

Abstract Obesity is a leading risk factor for premature mortality and poor medical outcomes due to its increasing global prevalence and its profound impact on the human body. Obesity also has a significant immune component as the establishment of a chronic inflammation in obese individuals is a significant driver of metabolic dysfunction. Additionally, obesity alters anti-tumor immunity, and it impairs protective antibody responses during infection or vaccination. The outcome can be extremely catastrophic, as highlighted in the COVID-19 pandemic with obese patients being particular susceptible to the disease. This relationship warrants more investigation into the obesity-associated changes occurring in B cells, central players in both the obesity-associated chronic inflammation and in the production of antibodies. Our lab has identified a subset of B cells which is expanded in both humans and mice during obesity and is characterized by the expression of the transcription factor T-bet. In vivostudies using obese mice fed a high fat diet revealed that these Tbet+ B cells promote inflammation and metabolic dysfunction through the production of proinflammatory antibodies. Additionally, blocking the expression of T-bet in the B cells of obese mice resulted in significant changes in antibody responses, with a greater expansion of germinal center B cells and an increased ability to generate antigen-specific B cells following immunization. Based on our findings, T-bet+ B cells represent an interesting link between obesity, inflammation, and antibody responses. Identifying the mechanisms regulating their function will provide new potential ways to reduce inflammation and enhance protection against infectious diseases in obese patients.