Cluster of differentiation 3 (CD3) is a multimeric protein complex that is essential for T cell activation and antigen recognition. It consists of five different polypeptide chains (γ, δ, ε, ζ, and η) that are noncovalently associated with the T cell receptor (TCR). The TCR is responsible for recognizing antigens presented by antigen-presenting cells (APCs), while CD3 transduces the activation signal into the T cell and activates helper T-cells and cytotoxic T-cells ^[1-2]. The CD3-TCR complex is expressed on the surface of all mature T cells, and its assembly is required for T cell development and function. CD3 plays a crucial role in stabilizing the TCR and facilitating its interaction with antigens. It also recruits signaling molecules to the TCR, which initiates a cascade of events that leads to T cell activation. CD3 is a highly specific T cell marker, and its expression is increased upon T cell activation. This makes it a valuable tool for identifying and characterizing T cells in tissues and blood samples. CD3 staining is also used to diagnose T-cell lymphomas and leukemias. Due to its essential role in T cell activation, CD3 is a promising target for immunosuppressive therapy. Several anti-CD3 monoclonal antibodies have been developed and are being tested in clinical trials for the treatment of autoimmune diseases, such as type 1 diabetes and rheumatoid arthritis ^[3].

The CD19 gene encodes a member of the immunoglobulin gene superfamily. As a key co-receptor in the B cell receptor (BCR) signaling pathway, it is crucial for B cell development, activation, and differentiation. CD19, a pan-B-cell marker exclusively expressed in the B cell lineage, remains stable throughout B cell development, from pro-B cells to mature and memory B cells. It acts as a positive regulator of BCR signal transduction by forming a B cell-specific signaling complex with CD21 (complement receptor 2), CD81 (tetraspanin), and CD225 (Leu13), which lowers the threshold for antigen-induced B cell activation ^[4]. Dysregulation of CD19 is strongly linked to autoimmune diseases such as systemic lupus erythematosus (SLE) and B cell malignancies like acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma. Mutations in this gene are associated with common variable immunodeficiency 3 (CVID3), characterized by impaired B cell differentiation and hypogammaglobulinemia. Owing to its B-cell-specific expression, CD19 has become a pivotal target for immunotherapy. For example, anti-CD19 CAR-T cell therapy (e.g., Tisagenlecleucel) has shown remarkable efficacy in refractory or relapsed ALL ^[5]. Recent studies have also explored CD19-targeted bispecific antibodies (e.g., blinatumomab) to enhance tumor cell clearance ^[6].

B6-hCD3/hCD19 mouse is a dual-gene humanized model generated by crossing B6-hCD3 mice (Catalog No.: C001325) with B6-hCD19 mice (Catalog No.: C001731). This strain is applicable for the development, validation, and preclinical evaluation of bispecific antibodies targeting human CD3/CD19, as well as for research on malignant tumors such as B-cell lymphoma and immunosuppressive therapies for autoimmune diseases. It serves as an ideal platform for the development of combination therapies.