Lulu Xu, Sheng Yang, Lifang Zhu, Zhicheng Mei, Wanning Li, Yunhui Chu, Xiaowei Pang, Hang Zhang, Shuhan Lu, Lian Chen, Jiayi He, Menglu Tian, Yuxin Liu, Luoqi Zhou, Ke Shang, Jun Xiao, Wei Wang, Daishi Tian, Chuan Qin
Ischemic white matter injury and the consequent neuroimmune response can contribute to vascular cognitive impairment. The role of B cells in ischemic white matter injury is unclear. Here, we show that crosstalk between meningeal B cells and CNS-resident microglia exacerbates white matter injury and vascular cognitive impairment. The B cell population expands and is activated in the dura mater, correlating with worsened white matter damage and neuroinflammation, whereas B cell depletion alleviates myelin thinning and cognitive impairment following chronic cerebral hypoperfusion in adult male mice. Mechanistically, microglia recruit meningeal B cells via MIF-CD74/CXCR4 signaling, and B cells adopt an IgG-secreting phenotype. IgG-secreting B cells induce microglial ferroptosis through Fc gamma receptors. Our data show that B cells contribute to white matter injury and cognitive impairment.