B6-hCD40LG Mouse

The CD40LG gene is located on the X chromosome (Xq26.3) and encodes CD40 ligand (CD40L, also known as CD154), a type II transmembrane protein mainly expressed on activated T cells, platelets, and some B cells. Under inflammatory conditions, monocytes, natural killer cells, mast cells, and basophils can also be induced to express CD40L ^[1-3]. This protein binds to CD40 on the surface of antigen-presenting cells (such as B cells and dendritic cells), mediating key immune functions including T cell-dependent B cell activation, immunoglobulin class switching, and germinal center formation ^[3]. The CD40/CD40L interaction also regulates thrombosis, inflammatory responses, hematopoiesis, and the tumor immune microenvironment. Abnormal regulation of CD40LG is associated with X-linked hyper-IgM syndrome (XHIGM), a primary immunodeficiency disease characterized by recurrent infections due to defective antibody production ^[4]. In addition, abnormal expression of CD40L is involved in diseases such as systemic lupus erythematosus and atherosclerosis through its pro-inflammatory effects ^[5-6]. Due to the important role of the CD40/CD40L interaction in immune activation, CD40/CD40L has been an important target for immunotherapy. In recent years, significant progress has been made in CD40/CD40L-targeted therapy. Various drugs have been developed, including agonistic/antagonistic monoclonal antibodies, cellular vaccines, adenoviral vectors, and protein antagonists, and have shown therapeutic potential in malignant tumors, autoimmune diseases, and allograft rejection ^[7].

The B6-hCD40LG mice are a humanized model constructed by using gene editing technology to replace the endogenous extracellular domain of the mouse Cd40lg gene with the extracellular domain of the human CD40LG gene. This model can be used for research on the disease mechanisms and treatment methods of autoimmune diseases, cardiovascular diseases, cancers, etc., as well as for CD40LG-targeted drug development.