Evidence indicates that lipid accumulation due to obesity triggers a low-grade, chronic inflammation, which is correlated with the occurrence of Type 2 diabetes (T2D). Recent studies provide evidence for the essential role that B cells play in obesity-induced inflammation and the development of insulin resistance. In visceral adipose tissue (VAT), B cells generate self-reactive antibodies (autoantibodies), which increase their pathogenicity. They also activate the production of cytokines by T cells through antigen presentation. Lastly, B cells themselves increase the production of inflammatory cytokines while decreasing the production of the anti-inflammatory cytokine IL-10. We hypothesize that neutral lipid accumulation exclusively in B cells will cause them to infiltrate VAT, trigger autoantibody production, and develop an autoimmune pathology. Preliminary research has led to the generation of a B cell-specific CGI-58 knockout (BKO) mice model in order to induce neutral lipid accumulation in B cells. It was found that increased accumulation of triglycerides in CGI-58 BKO mice significantly increased the levels of spontaneous activation in B cells, shown by the increases in the number of germinal center B cells, the surface expression levels of B cell activation markers, and the number of infiltrated lymphocytes in VAT, compared to Flox controls. The goal of this project is to determine the mechanism by which B cell lipid metabolism regulates B cell activation and pathogenicity in obesity-associated insulin resistance.