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

  • J Clin Invest. 2026 Mar 2;136(5):e196905. doi: 10.1172/JCI196905.
Sheng Yang  1  2  3 ,  Hang Zhang  1  2  3 ,  Lu-Lu Xu  1  2  3 ,  Luo-Qi Zhou  1  2  3 ,  Yun-Hui Chu  1  2  3 ,  Lian Chen  1  2  3 ,  Xiao-Wei Pang  1  2  3 ,  Lu-Yang Zhang  1  2  3 ,  Li-Fang Zhu  1  2  3 ,  Ming-Hao Dong  1  2  3 ,  Ke Shang  1  2  3 ,  Jun Xiao  1  2  3 ,  Long-Jun Wu  4 ,  Wei Wang  1  2  3 ,  Dai-Shi Tian  1  2  3 ,  Chuan Qin  1  2  3
Affiliations
  • 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.
PMID: 41766668 DOI: 10.1172/JCI196905
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
B cells; Immunology; Neuroscience.
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