Impact of Fli1 deletion on B cell populations: A focus on age-associated B cells and transcriptional dynamics

Abstract

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^+/-; Fli1^flox/flox) and Cd19-Cre^+/- mice were analyzed flow cytometrically. Transcriptional/epigenetic profiles of Cd11b⁺Cd11c⁺ ABCs were examined by RNA-sequencing and ATAC-sequencing.

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^+/- mice. Additionally, a striking increase in B-1 B cells, as well as Cd11b⁺Cd11c⁺ or T-bet⁺Cd11c⁺ ABCs, was observed in Fli1 BcKO mice. Furthermore, these mice exhibited elevated Cd138 levels in follicular B cells. Conducting transcriptional analyses of Fli1-depleted ABCs unveiled upregulated genes associated with cell-cell adhesion, coupled with downregulated genes linked to cell activation or immune responses. Exploring the chromatin landscape found that Fli1 depletion dysregulated the chromatin accessibility of the interferon regulatory factor family, implying potential roles in autoimmunity.

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.

Keywords: ATAC-seq; Cd138; Fli1; RNA-seq; age-associated B cell.