Hunan Key Laboratory of Cancer Metabolism, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
Key Laboratory of Carcinogenesis and Cancer Invasion of the Chinese Ministry of Education, NHC Key Laboratory of Carcinogenesis, Cancer Research Institute, School of Basic Medical Science, Central South University, Changsha, China.
J Hematol Oncol. 2021 Apr 7;14(1):58. doi: 10.1186/s13045-021-01074-6.
Lactoferrin (Lf) is widely distributed in mammalian milk, various tissues, and their exocrine fluids and has many physiological functions, such as bacteriostasis, antivirus, and immunoregulation. Here, we provide evidence that lactoferrin is required for early stages of B cell development in mice. Lactoferrin-deficient (Lf) C57BL/6 mice showed systematic reduction in total B cells, which was attributed to the arrest of early B cell development from pre-pro-B to pro-B stage. Although the Lf B cell "seeds" generated greater pro-B cells comparing to wild type (WT) littermates, the Lf mice bone marrow had less stromal cells, and lower CXCL12 expression, produced a less favorable "microenvironment" for early B cell development. The underlying mechanism was mediated through ERK and AKT signalings and an abnormality in the transcription factors related to early differentiation of B cells. The Lf mice also displayed abnormal antibody production in T cell-dependent and T cell-independent immunization experiments. In a pristane-induced lupus model, Lf mice had more serious symptoms than WT mice, whereas lactoferrin treatment alleviated these symptoms. This study demonstrates a novel role of lactoferrin in early B cell development, suggesting a potential benefit for using lactoferrin in B cell-related diseases.
乳铁蛋白（Lf）广泛分布于哺乳动物的乳汁、各种组织及其外分泌液中，具有多种生理功能，如抑菌、抗病毒和免疫调节。在这里，我们提供证据表明乳铁蛋白是小鼠 B 细胞早期发育所必需的。乳铁蛋白缺陷（Lf）C57BL/6 小鼠的总 B 细胞呈系统性减少，这归因于早期 B 细胞从前 B 细胞到 pro-B 细胞阶段的发育停滞。尽管 Lf B 细胞“种子”产生的 pro-B 细胞比野生型（WT）同窝仔鼠多，但 Lf 小鼠骨髓中的基质细胞较少，CXCL12 表达降低，为早期 B 细胞发育提供了较差的“微环境”。其潜在机制是通过 ERK 和 AKT 信号通路以及与 B 细胞早期分化相关的转录因子的异常来介导的。在 T 细胞依赖性和 T 细胞非依赖性免疫接种实验中，Lf 小鼠也表现出异常的抗体产生。在异丙醇诱导的狼疮模型中，Lf 小鼠的症状比 WT 小鼠更严重，而乳铁蛋白治疗减轻了这些症状。这项研究表明乳铁蛋白在早期 B 细胞发育中的新作用，提示乳铁蛋白在 B 细胞相关疾病中的应用具有潜在益处。
