Abstract
Regulatory B cells, specifically the CD24+CD38+ phenotype, are known for their capacity to reduce inflammation by releasing interleukin 10. However, their potential role in regulating inflammation through macrophage differentiation is not well understood. This study investigates how CD24+CD38+ regulatory B cells modulate the differentiation and function of pro-resolving macrophages through programmed death-ligand 1/programmed death-1 interactions and interleukin 10 secretion. Human CD24+CD38+ B cells were isolated from peripheral blood and co-cultured with THP-1-derived macrophages. Recombinant interleukin 10/ programmed death-ligand 1 and neutralizing antibodies were used to conduct gain and loss-of-function studies. Flow cytometry, quantitative PCR, and mass spectrometry were used to evaluate macrophage polarization, efferocytosis activity, and pro-resolving lipid mediator production. After co-culture, M2 polarization, programmed death-1 expression, and efferocytosis activity were increased significantly. Inhibition of either interleukin 10 or programmed death-ligand 1 pathway reduced M2 macrophage differentiation and functional activity. Co-culture of macrophages with CD24+CD38+ B cells enhanced the production of pro-resolving lipid mediators, particularly 12-HEPE and RvD5 through interleukin 10 secretion and programmed death-ligand 1/programmed death-1 ligation. These findings reveal a novel mechanism by which human CD24+CD38+ regulatory B cells promote macrophage-mediated resolution of inflammation through interleukin 10 secretion and programmed death-ligand 1/programmed death-1 ligation. By exploring how these regulatory pathways influence macrophage biology, we ultimately aim to uncover novel therapeutic targets for enhancing inflammation resolution in chronic inflammatory diseases.