Temporary CD19+ B Cell Inhibition Alleviates Ischemic Brain Damage in Mice

Abstract Ischemic stroke is a leading cause of death and disability worldwide, with limited treatment options available. Recent studies have shown that B cells play a critical role in the pathogenesis of ischemic stroke through their interaction with T cells in the meninges. In this study, we investigated whether temporary inhibition of B-cell activity through anti-CD19 antibody (aCD19 Ab) treatment could alleviate ischemic brain injury in a stroke mouse model by suppressing meningeal immunity. Methods Male C57BL/6 mice were subjected to transient middle cerebral artery occlusion (tMCAO) to induce focal ischemia. aCD19 Ab or Iso Ab was administered intraperitoneally 3 days prior to tMCAO. The mice were euthanized 24h after tMCAO for histological and immunological analyses. Other outcomes were assessed during the 7-day period. Results Compared to the MCAO/R group, treatment with Anti-CD19 Ab significantly reduced infarct size and brain edema, prolonged post-MCAO survival, and improved behavioral outcomes. Transmission electron microscope (TEM) and head Computed Tomography Angiography (CTA) results demonstrated that temporary B cell depletion led to improvements in microvascular endothelial edema, mitochondrial protection, reduced apoptosis, and enhanced post-MCAO cerebral vascular network reconstruction. Additionally, immune cells other than B cells decreased both in the brains (including brain parenchyma and meninges) and peripheral circulation of MCAO mice following B cell blockade, accompanied by decreased levels of cerebral parenchymal pro-inflammatory factors, including interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-alpha (TNF-α). The immune response alterations observed in the MCAO/R group were consistent with the trends indicated by stroke patient data. Conclusion Temporary inhibition of B-cell activity via aCD19 antibody injection may mitigate ischemic brain injury in a mouse model of stroke by suppressing systemic immune reactions. Changes in immune cells within the meninges play a role, and further investigation is needed to understand the mechanisms involved. These findings suggest that post-stroke local 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.