Lactoferrin is an iron-binding glycoprotein with a variety of physiological functions, and is widely existed in mammalian milk, neutrophils particles and various tissues and their exudates. It plays multiple roles in mammals, such as anti-microbial infection, anti-inflammation, iron transportation, and anti-tumorigenesis, all of which provide protective effects for the host.

As an innate immunity molecule, lactoferrin has many immune-regulatory functions, such as promoting antibody production, T-cell maturation, lymphocyte proliferation, activating natural killer cells and inhibiting mixed lymphocytes from releasing cytokines. Ma’s group previously reported that LF inhibits the growth and metastasis of human nasopharyngeal carcinoma cells thorough inhibiting AKT and MAPK signaling. Low expression or deletion of LF is closely related to the clinical stage and metastasis of nasopharyngeal carcinoma.

Through constructing a lactoferrin knockout mouse model (Lf^-/-), they provided evidence that lactoferrin is required for early stages of B cell development in mice. Lactoferrin-deficient 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 theLf^-/-B cell “seeds” generated greater pro-B cells comparing to WT littermates, theLf^-/-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. TheLf^-/-mice also displayed abnormal antibody production in T cell-dependent and -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.

Recently, this study has been reported in theJournal of Hematology & Oncology(PMID: 33827645). Ph.D. student Lingyu Wei is the first author, and Dr. Jian Ma (Cancer Research Institute of School of Basic Medical Science, Central South University) is thecorresponding author.