Carey, Anna2025-03-212025-03-212024-12https://hdl.handle.net/11299/270544University of Minnesota Ph.D. dissertation. December 2024. Major: Pharmacology. Advisor: Christina Camell. 1 computer file (PDF); xiii, 153 pages.Visceral white adipose tissue (VAT ) is a tissue to show early indications of aging including the upregulation of transcriptional pathways associated with inflammation and immune activation, shifting of the immune landscape, and metabolic dysfunction. B cells accumulate in VAT in response to inflammatory signals including IL-1b and were previously shown to promote metabolic dysfunction. The goal of this dissertation is to dissect mechanisms by which adipose B cells drive age-associated dysfunction and regulate their microenvironment in the VAT. We identified that non-canonical lipolysis induced by sepsis and endotoxemia, a metabolic process required for the regulation of inflammation, is impaired in the VAT of old mice. We found using a mouse model of life-long B cell deficiency that B cells drive impaired noncanonical lipolysis and pro-inflammatory macrophage phenotypes. We hypothesized that IL-1b may signal B cells to drive these phenotypes. To test this, we utilized an aging model of B cell selective IL1R1 knockout (BKO) and single cell RNA sequencing to investigate the contribution of this signaling pathway to aged VAT immune cell inflammatory profiles. We identified that IL-1b signaling on B cells results in differentially affected immune cell populations including the immunosuppression of MHCIIhi inflammatory macrophages that increase during aging. Finally, we describe how B cell-macrophage dependent production of TGFb likely drives the suppression of noncanonical lipolysis in the VAT of old mice. Overall, the data presented in this dissertation outline how adipose B cells and macrophage crosstalk regulates VAT aging to promote metabolic dysfunction and inflammation but also has nuanced immunosuppressive roles in response to specific signals including IL-1b. We propose that the B cell-macrophage signaling axis in the VAT is an appealing therapeutic target to improve metabolism, ameliorate age-associated inflammation, and reduce mortality during infections in elderly populations.enAdipose tissueAgingB cellsImmunometabolismMacrophagesSepsisThesis or Dissertation