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

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

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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