CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage
BackgroundIschemic stroke, accounting for approximately 80% of all stroke cases, is a major public health challenge and a leading cause of death and disability worldwide. Current treatments primarily involve thrombolytic therapy, limited to a 4.5-hour window due to the risk of complications, undersc...
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Frontiers Media S.A.
2025-04-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528471/full |
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| author | Yu Xu Yu Xu Jing Peng Yizhong Yan Min Gao HongJing Zang Lamei Cheng Lamei Cheng Lamei Cheng Yu Zhou Yu Zhou Yu Zhou |
| author_facet | Yu Xu Yu Xu Jing Peng Yizhong Yan Min Gao HongJing Zang Lamei Cheng Lamei Cheng Lamei Cheng Yu Zhou Yu Zhou Yu Zhou |
| author_sort | Yu Xu |
| collection | DOAJ |
| description | BackgroundIschemic stroke, accounting for approximately 80% of all stroke cases, is a major public health challenge and a leading cause of death and disability worldwide. Current treatments primarily involve thrombolytic therapy, limited to a 4.5-hour window due to the risk of complications, underscoring the need for new therapeutic targets. Systemic inflammation plays a critical role in stroke progression, with immune cells infiltrating the brain and exacerbating damage. B cells, in particular, have been implicated in stroke pathogenesis, although their exact role remains contentious. This study examines anti-CD19 antibody (aCD19 Ab) treatment in a stroke model to determine if CD19+ B cell depletion can reduce infarct size and alleviate inflammation.ResultsThis study investigated whether temporary inhibition of B-cell activity using an aCD19 Ab could alleviate ischemic brain injury in a stroke mouse model by regulating cerebral and systemic immune reactions. Mice subjected to middle cerebral artery occlusion (MCAO) exhibited significant reductions in infarct size and brain edema, prolonged post-MCAO survival, and improved behavioral outcomes following aCD19 Ab treatment. Transmission electron microscopy (TEM) and Computed Tomography Angiography (CTA) results revealed a reduction in microvascular endothelial edema, decreased mitochondrial damage in neurons, reduced neuronal apoptosis, and a favorable reconstruction of the cerebral vascular network. Additionally, B cell inhibition reduced pro-inflammatory cytokines and immune cells in the brain and peripheral circulation. The immune response alterations observed in the MCAO/R group were consistent with the trends indicated by stroke patient data.ConclusionsTemporary inhibition of B-cell activity via aCD19 antibody injection alleviated ischemic brain injury in a mouse model of stroke by suppressing systemic immune reactions. Changes in immune cells within the meninges may play a role, and further investigation is needed to understand the mechanisms involved. These findings suggest that cerebral and systemic immune responses contribute to the pathogenesis of ischemic stroke, and temporary B cell depletion may represent a potential therapeutic target for stroke therapy. |
| format | Article |
| id | doaj-art-2a7aaae67eb84c58b33d3c00019c6b01 |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-2a7aaae67eb84c58b33d3c00019c6b012025-08-20T02:12:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-04-011610.3389/fimmu.2025.15284711528471CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damageYu Xu0Yu Xu1Jing Peng2Yizhong Yan3Min Gao4HongJing Zang5Lamei Cheng6Lamei Cheng7Lamei Cheng8Yu Zhou9Yu Zhou10Yu Zhou11Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, ChinaNational Engineering Research Center of Human Stem Cell, Changsha, ChinaNational Engineering Research Center of Human Stem Cell, Changsha, ChinaDepartment of Radiology, The Second Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Pathology, The Second Xiangya Hospital of Central South University, Changsha, ChinaInstitute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, Changsha, ChinaNational Engineering Research Center of Human Stem Cell, Changsha, ChinaHunan Guangxiu Hi-tech Life Technology Co. Ltd, Changsha, ChinaDepartment of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, ChinaNational Engineering Research Center of Human Stem Cell, Changsha, ChinaHunan Guangxiu Hi-tech Life Technology Co. Ltd, Changsha, ChinaBackgroundIschemic stroke, accounting for approximately 80% of all stroke cases, is a major public health challenge and a leading cause of death and disability worldwide. Current treatments primarily involve thrombolytic therapy, limited to a 4.5-hour window due to the risk of complications, underscoring the need for new therapeutic targets. Systemic inflammation plays a critical role in stroke progression, with immune cells infiltrating the brain and exacerbating damage. B cells, in particular, have been implicated in stroke pathogenesis, although their exact role remains contentious. This study examines anti-CD19 antibody (aCD19 Ab) treatment in a stroke model to determine if CD19+ B cell depletion can reduce infarct size and alleviate inflammation.ResultsThis study investigated whether temporary inhibition of B-cell activity using an aCD19 Ab could alleviate ischemic brain injury in a stroke mouse model by regulating cerebral and systemic immune reactions. Mice subjected to middle cerebral artery occlusion (MCAO) exhibited significant reductions in infarct size and brain edema, prolonged post-MCAO survival, and improved behavioral outcomes following aCD19 Ab treatment. Transmission electron microscopy (TEM) and Computed Tomography Angiography (CTA) results revealed a reduction in microvascular endothelial edema, decreased mitochondrial damage in neurons, reduced neuronal apoptosis, and a favorable reconstruction of the cerebral vascular network. Additionally, B cell inhibition reduced pro-inflammatory cytokines and immune cells in the brain and peripheral circulation. The immune response alterations observed in the MCAO/R group were consistent with the trends indicated by stroke patient data.ConclusionsTemporary inhibition of B-cell activity via aCD19 antibody injection alleviated ischemic brain injury in a mouse model of stroke by suppressing systemic immune reactions. Changes in immune cells within the meninges may play a role, and further investigation is needed to understand the mechanisms involved. These findings suggest that cerebral and systemic immune responses contribute to the pathogenesis of ischemic stroke, and temporary B cell depletion may represent a potential therapeutic target for stroke therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528471/fullischemic strokeB cellsanti-CD19 antibodyinflammationmeningeal immunity |
| spellingShingle | Yu Xu Yu Xu Jing Peng Yizhong Yan Min Gao HongJing Zang Lamei Cheng Lamei Cheng Lamei Cheng Yu Zhou Yu Zhou Yu Zhou CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage Frontiers in Immunology ischemic stroke B cells anti-CD19 antibody inflammation meningeal immunity |
| title | CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage |
| title_full | CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage |
| title_fullStr | CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage |
| title_full_unstemmed | CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage |
| title_short | CD19+ B cell depletion: a novel strategy to alleviate ischemic stroke damage |
| title_sort | cd19 b cell depletion a novel strategy to alleviate ischemic stroke damage |
| topic | ischemic stroke B cells anti-CD19 antibody inflammation meningeal immunity |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1528471/full |
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