Activated CD4+ T cells upregulate PD-L1 expression on B cells through CD40/CD40L signaling and direct contact in systemic lupus erythematosus

Abstract

Programmed cell death protein 1 (PD-1) expression on T cells has been implicated in the pathogenesis of autoimmune diseases; however, the functional role of programmed death-ligand 1 (PD-L1) expression on B cells remains insufficiently characterized, particularly in the context of CD4⁺ T cell–mediated regulation in systemic lupus erythematosus (SLE). Flow cytometric analysis revealed that PD-L1⁺ B cells exhibited upregulated surface expression of the co-stimulatory molecules CD80 and CD86, alongside a concomitant downregulation in the expression of the antigen-presenting molecule human leukocyte antigen DR (HLA-DR). Furthermore, an elevated frequency of class-switched PD-L1⁺ B cells was observed in the peripheral blood of patients with SLE. Using co-culture systems and transwell assays, we demonstrated that CD4⁺ T cells modulate PD-L1 expression on B cells via direct cell–cell interactions. Mechanistically, this regulation was shown to be dependent on bidirectional CD40/CD40L signaling. These findings advance our understanding of PD-L1-mediated immunoregulation in SLE pathogenesis and identify PD-L1⁺ B cells as potential targets for therapeutic intervention.