Ligand-receptor interactions induce and mediate regulatory functions of BATF3+ B cells

B cells express protein ligands, whose potential regulatory functions remain incompletely understood. Here, we profiled the ligand expression in murine B sub-lineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities by analyzing ligand-receptor interactions in silico. We identified a B subset for their specific expression of cytokine IL-27 and chemokine CXCL10. Through the IL-27-IL-27 receptor interaction, IL-27/CXCL10-producing B cells targeted CD40-activated B cells in vitro and, upon induction by immunization and viral infection, optimized antibody responses and anti-viral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction-mediated self-targeting, they promoted B-cell PD-L1 expression and immune evasion. Mechanistically, Il27 and Cxcl10 transcription was induced by synergizing TLR and CD40 signals and mediated by co-induced transcription factor (TF) BATF3, which directly targeted these genes. By utilizing a framework focusing on discovering regulatory cells and their hallmark TFs, our findings have broadened the scope of B cell regulatory functions.