Faculty, Staff and Student Publications
Language
English
Publication Date
10-10-2025
Journal
Science Advances
DOI
10.1126/sciadv.adx9917
PMID
41061049
PMCID
PMC12506935
PubMedCentral® Posted Date
10-8-2025
PubMedCentral® Full Text Version
Post-print
Abstract
B cells express many protein ligands, yet their regulatory functions are incompletely understood. We profiled ligand expression across murine B sublineage cells, including those activated by defined receptor signals, and assessed their regulatory capacities and specificities through in silico analysis of ligand-receptor interactions. Consequently, we identified a B cell subset that expressed cytokine interleukin-27 (IL-27) and chemokine CXCL10. Through the IL-27–IL-27 receptor interaction, these 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 antiviral immunity in vivo. Also present in breast cancer tumors and retained there through CXCL10-CXCR3 interaction–mediated self-targeting, these cells promoted B cell PD-L1 expression and immune evasion. Mechanistically, Il27 and Cxcl10 transcription was induced by synergizing Toll-like receptor (TLR) and CD40 signals and driven by coinduced transcription factor BATF3, which directly targeted these genes. By applying a discovery framework focusing on regulatory cells, our findings expand the recognized scope of B cell regulatory functions.
Keywords
Animals, Basic-Leucine Zipper Transcription Factors, Mice, Chemokine CXCL10, B-Lymphocytes, Ligands, Repressor Proteins, CD40 Antigens, Receptors, CXCR3, Signal Transduction, Humans, Female, Interleukins, Protein Binding
Published Open-Access
yes
Recommended Citation
Yan, Hui; Wang, Rui; Viswanadhapalli, Suryavathi; et al., "Ligand-Receptor Interactions Induce and Mediate Regulatory Functions of BATF3+ B Cells" (2025). Faculty, Staff and Student Publications. 1207.
https://digitalcommons.library.tmc.edu/uthsph_docs/1207