Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage via MIF-CD74/CXCR4 and Interferon Signaling

Authors

Sheng Yang
Hang Zhang
Lu-Lu Xu
Luo-Qi Zhou
Yun-Hui Chu
Lian Chen
Xiao-Wei Pang
Lu-Yang Zhang
Li-Fang Zhu
Ming-Hao Dong
Ke Shang
Jun Xiao
Long-Jun Wu
Wei Wang
Dai-Shi Tian
Chuan Qin

Language

English

Publication Date

3-2-2026

Journal

Journal of Clinical Investigation

DOI

10.1172/JCI196905

PMID

41766668

PMCID

PMC12948440

PubMedCentral® Posted Date

3-2-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Neuroinflammation, encompassing both innate and adaptive immune responses, plays a crucial role in ischemic stroke. Although B lymphocytes are central to adaptive immunity, their contributions to ischemic stroke remain poorly understood. Here, we demonstrated that B lymphocytes accumulate in ischemic lesions, forming germinal center-like structures at the later stage after stroke, which mainly depended on in situ proliferation. This accumulation correlated with worsened neuroinflammation and ischemic injury, whereas B cell depletion reduced chronic brain damage during stroke. Mechanistically, microglia recruited B cells into ischemic lesions through MIF-CD74/CXCR4 signaling during the early phase of stroke, while IFN-related pathways in B cells further drove neuroinflammation and brain injury. Targeting these pathways markedly alleviated cerebral ischemia and inflammation. Our findings shed light on the role of B lymphocytes in stroke pathology and suggest promising new avenues for therapeutic intervention.

Keywords

Animals, Mice, Macrophage Migration-Inhibitory Factors, Antigens, Differentiation, B-Lymphocyte, B-Lymphocytes, Signal Transduction, Histocompatibility Antigens Class II, Receptors, CXCR4, Intramolecular Oxidoreductases, Male, Interferons, Brain Ischemia, Mice, Knockout, Mice, Inbred C57BL, Humans, Immunology, Neuroscience, B cells

Published Open-Access

yes

Recommended Citation

Yang, Sheng; Zhang, Hang; Xu, Lu-Lu; et al., "Ectopic B Lymphocyte Follicles Exacerbate Ischemic Brain Damage via MIF-CD74/CXCR4 and Interferon Signaling" (2026). Faculty, Staff and Student Publications. 6703.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6703