CD19 is predominantly expressed throughout B-cell development and serves as a critical co-receptor for B-cell receptor (BCR) signal transduction, participating in B-cell development, activation, and differentiation ^[1]. The TNFRSF17 gene encodes B-cell maturation antigen (BCMA), a member of the tumor necrosis factor receptor superfamily. BCMA is primarily expressed on mature B cells and plasma cells and acts as a key regulator for maintaining plasma cell survival, antibody secretion, and humoral immunity ^[2-3]. The huCD19/huBCMA(TNFRSF17) mouse is a dual-gene humanized model obtained by crossing the huCD19 mouse (Catalog No.: C001731) with the huBCMA(TNFRSF17) mouse (Catalog No.: C001630). These two targets cover the critical stages of B-cell development and plasma cell maturation, respectively, together forming an important regulatory network for B-cell immune responses. This model can be used to study the mechanisms of B-cell development, differentiation, and humoral immunity regulation, as well as B-cell-related autoimmune diseases and malignancies, such as systemic lupus erythematosus (SLE) and multiple myeloma (MM). It is also suitable for the screening, pharmacodynamic evaluation, safety assessment, and mechanism-of-action studies of anti-CD19 and anti-BCMA dual-target drugs, CAR-T cell therapies, bispecific antibodies, and combination treatment strategies, providing an ideal preclinical research platform for the development of innovative therapies for B-cell-related diseases.

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 TNFRSF17 gene, also known as BCMA, encodes a protein belonging to the tumor necrosis factor receptor superfamily. This protein is predominantly expressed in mature B lymphocytes, particularly plasma cells, with lower expression in early B cells and non-B cells ^[4-5]. As a type III transmembrane glycoprotein, TNFRSF17 plays a critical role in B cell survival and differentiation, acting as a key regulator of B cell maturation ^[5]. Functionally, TNFRSF17 primarily acts as a receptor for the B cell-activating factor (BAFF). Upon BAFF binding, it activates both the classical NF-κB pathway and the non-classical MAPK8/JNK pathway, subsequently regulating downstream gene expression to promote B cell survival, proliferation, and antibody secretion. Furthermore, TNFRSF17 can interact with TNFR-associated factors (TRAFs) 1, 2, and 3, further mediating physiological processes related to cell differentiation and growth ^[4-5]. Multiple studies have demonstrated that the TNFRSF17 gene and its protein are associated with various B cell-related diseases. Notably, this gene exhibits abnormally high expression in diseases such as multiple myeloma and systemic lupus erythematosus, rendering it a potential therapeutic target for these conditions ^[6-7]. The B6-hCD3/hBCMA mouse is a dual-gene humanized model generated by crossing B6-hCD3 mice (Catalog No.: C001325) with B6-hBCMA (TNFRSF17) mice (Catalog No.: C001630). This model can be used for researching the pathological mechanisms and therapeutic approaches of diseases such as autoimmune diseases and multiple myeloma, as well as for the development of CD3/BCMA-targeted drugs.

Complement component C3 plays a central role in activating the complement system and is the most abundant complement protein in human plasma, primarily synthesized in the liver. As part of the innate immune system, the complement system is activated during tissue damage and pathogen invasion, playing a crucial role in the inflammatory response, host homeostasis, and pathogen defense. The complement cascade is activated through the classical pathway, alternative pathway, and lectin pathway, all of which generate C3 convertase, which cleaves C3 into C3a and C3b. C3a is a potent anaphylatoxin with pro-inflammatory activity, while C3b is a regulator that induces C5 cleavage, thereby participating in the dissolution and clearance of immune complexes. Mutations in this gene are associated with atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). Deficiencies in C3 and C3-derived peptides can lead to autoimmune diseases (such as rheumatoid arthritis, systemic lupus erythematosus, and vasculitis) and make individuals susceptible to recurrent respiratory infections and infections caused by encapsulated organisms. Conversely, excessive activation of C3 and related complement components is associated with kidney diseases (immune complex glomerulonephritis, hemolytic uremic syndrome, lupus nephritis, membranous nephropathy, and immune-mediated nephropathy) ^[1-2]. The Transferrin receptor (TFRC) gene encodes Transferrin Receptor 1 (TFR1), a protein that is expressed at low levels in most normal cells but shows increased expression in highly proliferative cells, such as basal epidermal cells, intestinal epithelium, and certain activated immune cells. Brain capillary endothelial cells, which constitute the blood-brain barrier (BBB), also express this receptor at high levels ^[3]. TFR1 plays a critical role in maintaining iron metabolism and homeostasis by facilitating receptor-mediated endocytosis of iron-bound transferrin (Tf) via Tf cycling, thereby promoting iron uptake ^[4]. Cellular iron deficiency can lead to apoptosis, while cellular transformation requires substantial iron to sustain proliferation, with iron overload contributing to tumor progression. The high expression of TFR1 in many tumors makes it a potential tumor marker, offering a target for therapies to inhibit tumor growth and metastasis ^[3]. Moreover, TFR1 is implicated in anemia and iron metabolism disorders. Studies have shown that elevated TFR1 expression in cardiomyocytes is associated with exacerbated inflammation in myocarditis patients ^[5]. Various clinical drugs targeting TFR1 are currently under development, including antisense oligonucleotides (ASOs), antibody-drug conjugates (ADCs), and antibody-oligonucleotide conjugates, applicable to diseases such as cancer, anemia, and neurodegenerative disorders. Research indicates that enhancing antibody transport across the blood-brain barrier via TFR1, by forming specific bispecific antibodies with anti-β-amyloid antibodies, can improve therapeutic outcomes in Alzheimer's patients ^[6-7]. As research progresses, TFR1 is expected to become an effective clinical target for multiple diseases and a synergistic target for drug delivery across the blood-brain barrier (BBB). The hTFRC/huC3 mouse model is a humanized model obtained by breeding huC3 mice (Catalog No.: C001955) with hTFRC mice (Catalog No.: C001584). This model can be used for research on complement-mediated diseases, iron metabolism disorders, neurodegenerative diseases, and tumor development, aiding in studying C3/TFRC-targeted drugs.

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]. The TNFRSF17 gene, also known as BCMA, encodes a protein belonging to the tumor necrosis factor receptor superfamily. This protein is predominantly expressed in mature B lymphocytes, particularly plasma cells, with lower expression in early B cells and non-B cells ^[7-8]. As a type III transmembrane glycoprotein, TNFRSF17 plays a critical role in B cell survival and differentiation, acting as a key regulator of B cell maturation ^[8]. Functionally, TNFRSF17 primarily acts as a receptor for the B cell-activating factor (BAFF). Upon BAFF binding, it activates both the classical NF-κB pathway and the non-classical MAPK8/JNK pathway, subsequently regulating downstream gene expression to promote B cell survival, proliferation, and antibody secretion. Furthermore, TNFRSF17 can interact with TNFR-associated factors (TRAFs) 1, 2, and 3, further mediating physiological processes related to cell differentiation and growth ^[7-8]. Multiple studies have demonstrated that the TNFRSF17 gene and its protein are associated with various B cell-related diseases. Notably, this gene exhibits abnormally high expression in diseases such as multiple myeloma and systemic lupus erythematosus, rendering it a potential therapeutic target for these conditions ^[9-10]. The B6-hCD3/hCD19/hBCMA mouse is a tri-gene humanized model generated by crossing B6-hCD3 mice (Catalog No.: C001325), B6-hCD19 mice (Catalog No.: C001731), and B6-hBCMA (hTNFRSF17) mice (Catalog No.: C001630). This model can be used for the research of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), as well as B-cell malignancies, and for the development, screening, and preclinical evaluation of related targeted therapeutics.