Ligand-receptor interactions induce and mediate regulatory functions of BATF3 <sup>+</sup> B cells

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, <i>Il27</i> and <i>Cxcl10</i> 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.

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Publication Details

Journal
Science Advances
Published
2025-10-08
DOI
https://doi.org/10.1126/sciadv.adx9917
Citations
1
Primary Topic
Immune Cell Function and Interaction
Type
article
Field-Weighted Citation Impact
0.80
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article

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

Christopher A. Hunter, Siyuan Zheng, Dariela Perez, Carlos Eduardo Rivera et al.
1 citations
Science Advances
Immune Cell Function and Interaction
0.80
article

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

Christopher A. Hunter, Siyuan Zheng, Dariela Perez, Carlos Eduardo Rivera, Harshita B. Gupta, Hui Yan, Mustafa Khan, Booki Min, E. Wang, Weiwei Luo, Evelien M. Bunnik, María E. Fernández, Suryavathi Viswanadhapalli, Hong Zan, Paolo Casali, Gangadhara R. Sareddy, Diako Ebrahimi, Uday P. Pratap, Ross M. Kedl, Zhenming Xu, Yan Xiang, Tyler Jay Curiel, Zhinan Yin, Azad Khosh, Guangming Zhong, Fushun Zhang, Ratna K. Vadlamudi, Christian Cervantes, Funan He, Jingwei Wang, Rui Wang, Yidong Chen, Xiao-Dong Li, Shuai Wu, Zhenqing Ye, Li Yue, Karli Hinton, Sai Eashan Vankamamidi
article en
1 citations

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, <i>Il27</i> and <i>Cxcl10</i> 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.

Science AdvancesVol. 11(41)
Dartmouth College (US), Northwestern University (US), Texas Biomedical Research Institute (US), Central South University (CN), Jinan University (CN), Murphy Oil Corporation (United States) (US), Urology San Antonio (US), Children's Hospital of San Antonio (US), South Texas Veterans Health Care System (US), Second Xiangya Hospital of Central South University (CN), Third Xiangya Hospital (CN), Xiangya Hospital Central South University (CN), The University of Texas at San Antonio (US), University of Colorado Anschutz Medical Campus (US), University of Pennsylvania (US)
Openalex Percentile: Top 23%
Immune Cell Function and Interaction
0.80
DOIOpen Access PDFOpenAlex
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