A novel phenotype of B cells associated with enhanced phagocytic capability and chemotactic function after ischemic stroke

作者：Rui Wang, Huaming Li, Chenhan Ling, Xiaotao Zhang, Jianan Lü, Weimin Luan, Jianmin Zhang, Ligen Shi · 发表于：Neural Regeneration Research · 年份：2023 · DOI：10.4103/1673-5374.371365 · 被引用次数：31 · 研究领域：Neuroinflammation and Neurodegeneration Mechanisms、Immune cells in cancer、Immune Response and Inflammation

Accumulating evidence has demonstrated the involvement of B cells in neuroinflammation and neuroregeneration. However, the role of B cells in ischemic stroke remains unclear. In this study, we identified a novel phenotype of macrophage-like B cells in brain-infiltrating immune cells expressing a high level of CD45. Macrophage-like B cells characterized by co-expression of B-cell and macrophage markers, showed stronger phagocytic and chemotactic functions compared with other B cells and showed upregulated expression of phagocytosis-related genes. Gene Ontology analysis found that the expression of genes associated with phagocytosis, including phagosome- and lysosome-related genes, was upregulated in macrophage-like B cells. The phagocytic activity of macrophage-like B cells was verified by immunostaining and three-dimensional reconstruction, in which TREM2-labeled macrophage-like B cells enwrapped and internalized myelin debris after cerebral ischemia. Cell-cell interaction analysis revealed that macrophage-like B cells released multiple chemokines to recruit peripheral immune cells mainly via CCL pathways. Single-cell RNA sequencing showed that the transdifferentiation to macrophage-like B cells may be induced by specific upregulation of the transcription factor CEBP family to the myeloid lineage and/or by downregulation of the transcription factor Pax5 to the lymphoid lineage. Furthermore, this distinct B cell phenotype was detected in brain tissues from mice or patients wit...