BACKGROUND: Altered Fli1 expression is associated with various autoimmune diseases, yet its impact on B cells remains unexplored. OBJECTIVE: This study investigated the direct effects of Fli1 depletion on B cell populations, focusing on age-associated B cells (ABCs). METHODS: Splenocytes of Fli1 BcKO (Cd19-Cre RESULTS: Fli1 BcKO mice displayed a notable reduction in follicular and marginal zone B cells, with a concurrent rise in newly formed B cells compared to Cd19-Cre CONCLUSION: These findings suggest complex modulations of B cell populations and immune-related gene expression due to Fli1 deficiency, shedding light on its involvement in autoimmune processes.