CD36-mediated metabolic changes in Tbet+CD11c+ B cell during obesity 2309773

Abstract

Abstract Introduction CD21- CD23- CD11c+ Tbet+ B cells expand in primary immune and peripheral tissues during chronic conditions such as aging, autoimmune diseases, and obesity. CD11c+ Tbet+ B cells are a class-switched, antigen-specific memory population that exhibit a distinct transcriptomic profile from other B cell subsets characterized primarily by enrichment of metabolism and cytokine pathways. Our previous study demonstrated that transfer of T-bet + B cells exacerbates metabolic syndrome during obesity. In addition, CD36 is a scavenger receptor expressed highly in CD11c+ T-bet+ B cells which also mediates oxLDL-induced metabolic reprogramming from OXPHOS toward glycolysis in macrophages. Methods This project uses cutting-edge approaches, including SCENITH and single-cell RNA sequencing, combine with flow cytometry based metabolic analyses to comprehensively characterize metabolic pathways in CD11c+ T-bet+ B cells at the molecular level. In parallel, a high-fat diet in a unique mouse model with B cell specific CD36 deletion, allows us to define the role of CD36 in mediating metabolic reprogramming in CD11c+ T-bet+ B cells during obesity. Results Our preliminary data show that CD36 knockdown in B cells markedly reduces CD11c+Tbet+ B expansion and lowers circulating anti-oxLDL autoantibody levels in both HFD fed and R848-immunized mice. Assessment of alterations in glycolytic and oxidative phosphorylation pathways, mitochondrial morphology, mass, and function, help us to define the transcriptomic profiles of CD11c+ T-bet+ B cells during obesity, while determining how B cell specific CD36 deletion modulates these metabolic programs. Conclusion Overall, defining the role of CD36 in driving metabolic reprogramming of CD11c+ T-bet+ B cells during disease progression will provide critical insights for the development of therapies that selectively target defined cellular pathways. Funding Source The Flow Cytometry Shared Resource at UT Health San Antonio is supported by the National Cancer Institute (P30CA054174) through the Mays Cancer Center, the Cancer Prevention and Research Institute of Texas (CPRIT) (RP210126), the National Institutes of He Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)