OSCR

Ectopic B lymphocyte follicles exacerbate ischemic brain damage via MIF-CD74/CXCR4 and interferon signaling.

Overview

Authors: Sheng Yang1,2,3, Hang Zhang1,2,3, Lu-Lu Xu1,2,3, Luo-Qi Zhou1,2,3, Yun-Hui Chu1,2,3, Lian Chen1,2,3, Xiao-Wei Pang1,2,3, Lu-Yang Zhang1,2,3, Li-Fang Zhu1,2,3, Ming-Hao Dong1,2,3, Ke Shang1,2,3, Jun Xiao1,2,3, Long-Jun Wu4, Wei Wang1,2,3, Dai-Shi Tian1,2,3, Chuan Qin1,2,3
ORCID iDs: Long-Jun Wu
  1. Department of Neurology, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases
  2. Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital of Tongji Medical College; and
  3. Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, Hubei, China
  4. Center for Neuroimmunology and Glial Biology, Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA
Institutions: Tongji Hospital (China); Huazhong University of Science and Technology (China); The University of Texas Health Science Center at Houston (United States)
Journal: The Journal of clinical investigation, volume 136, issue 5, article e196905
Dates: received 17 June 2025; accepted 4 December 2025; published online 2 March 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1172/jci196905 · PMID 41766668 · PMCID PMC12948440 · OpenAlex W7132817227
Open access: gold, a free copy (OpenAlex)
Status: data only
Categories: mouse (organism), stroke (population), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Machine learning, fMRI & imaging
Keywords: Immunology, Neuroscience, B cells
MeSH: Antigens, Differentiation, B-Lymphocyte*, B-Lymphocytes*, Brain Ischemia*, Interferons*, Intramolecular Oxidoreductases*, Macrophage Migration-Inhibitory Factors*, Receptors, CXCR4*, Signal Transduction*, Animals, Histocompatibility Antigens Class II, Male, Mice, Mice, Knockout (* major topic)
Topic: Macrophage Migration Inhibitory Factor (Immunology, Immunology and Microbiology), according to OpenAlex
Funding: National Natural Science Foundation of China (82271341, 81873743, 82371404, 82401565); Ministry of Science and Technology China Brain Initiative Grant (STI2030-Major Projects 2022ZD0204700); Key Research and Development Program of Hubei Provincial Department of Science and Technology (2023BCB148)
Citations: cited by 3 papers (Europe PMC); 54 references in the paper

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper links to its data, not to its authors' code: see the Data section.

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Data

Datasets cited

Data availability

The data for RNA-seq in this paper are deposited into NCBI SRA database with the accession number PRJNA1337929. All data in this paper are available from the corresponding authors upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 16 authors, 3 keywords, 13 MeSH terms, 3 funders, 54 references.

Cite

This paper

Yang, S., Zhang, H., Xu, L.-L., Zhou, L.-Q., Chu, Y.-H., Chen, L., Pang, X.-W., Zhang, L.-Y., Zhu, L.-F., Dong, M.-H., Shang, K., Xiao, J., Wu, L.-J., Wang, W., Tian, D.-S., & Qin, C. (2026). Ectopic B lymphocyte follicles exacerbate ischemic brain damage via MIF-CD74/CXCR4 and interferon signaling. The Journal of clinical investigation, 136(5), e196905. https://doi.org/10.1172/jci196905

BibTeX

@article{yang2026ectopic,
author = {Yang, Sheng and Zhang, Hang and Xu, Lu-Lu and Zhou, Luo-Qi and Chu, Yun-Hui and Chen, Lian and Pang, Xiao-Wei and Zhang, Lu-Yang and Zhu, Li-Fang and Dong, Ming-Hao and Shang, Ke and Xiao, Jun and Wu, Long-Jun and Wang, Wei and Tian, Dai-Shi and Qin, Chuan},
title = {{Ectopic B lymphocyte follicles exacerbate ischemic brain damage via MIF-CD74/CXCR4 and interferon signaling}},
journal = {The Journal of clinical investigation},
year = {2026},
month = mar,
volume = {136},
number = {5},
pages = {e196905},
publisher = {American Society for Clinical Investigation},
issn = {0021-9738},
doi = {10.1172/jci196905},
url = {https://doi.org/10.1172/jci196905},
pmid = {41766668},
pmcid = {PMC12948440}
}

RIS

TY - JOUR
AU - Yang, Sheng
AU - Zhang, Hang
AU - Xu, Lu-Lu
AU - Zhou, Luo-Qi
AU - Chu, Yun-Hui
AU - Chen, Lian
AU - Pang, Xiao-Wei
AU - Zhang, Lu-Yang
AU - Zhu, Li-Fang
AU - Dong, Ming-Hao
AU - Shang, Ke
AU - Xiao, Jun
AU - Wu, Long-Jun
AU - Wang, Wei
AU - Tian, Dai-Shi
AU - Qin, Chuan
TI - Ectopic B lymphocyte follicles exacerbate ischemic brain damage via MIF-CD74/CXCR4 and interferon signaling
T2 - The Journal of clinical investigation
J2 - J Clin Invest
PY - 2026
DA - 2026/03/02
VL - 136
IS - 5
SP - e196905
SN - 0021-9738
PB - American Society for Clinical Investigation
DO - 10.1172/jci196905
UR - https://doi.org/10.1172/jci196905
LA - en
ER -

CSL-JSON

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