PhD candidate University of Texas Health Science Center, San Antonio San Antonio, Texas, United States
Introduction/Rationale: 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.
