Dysfunction in B cell tolerance and activation in obesity.

Abstract Obesity is a complex condition that affects a large part of the global population, making it a major risk factor for premature mortality and medical complications. Obesity profoundly engages the immune system, impacting cancer immunity, infections, and autoimmunity. Additionally, obesity is associated with a low-grade chronic inflammation which exacerbates metabolic dysfunction. B cells play a significant role in obesity-associated inflammation and metabolic dysfunction, but their effect is subset-dependent and can be either protective or pathogenic. Therefore, understanding how different B cell populations contribute to these phenotypes represent a crucial goal. Our lab has identified a subset of B lymphocytes which is expanded in the adipose tissue of humans and mice during obesity. These B cells co-express the transcription factor T-bet and the integrin CD11c, and they produce IgG2c antibodies. In vivo studies with mice fed a high fat diet revealed that these Tbet+ B cells promote inflammation through the production of proinflammatory antibodies. Additionally, these B cells express high levels of the scavenger receptor CD36, a lipid-transport molecule associated with inflammation and atherosclerosis. As a potential consequence of the CD36 expression, the Tbet+ B cells maintain a higher intracellular lipid content and are capable of increased uptake of oxidized LDL compared to conventional B cells, suggesting a unique lipid metabolism. Because of their unique nature, T-bet+ B cells represent a potential link between obesity, inflammation, and autoimmunity. Identifying the mechanisms regulating their function will provide new potential targets to reduce inflammation and immunological dysfunction in obese patients. Supported by R01 AI132798