The novel B6-Igl Knockout (KO) mouse model exclusively expresses κ light chain immunoglobulins, offering researchers a powerful tool for exploring B cell development and antibody diversity. This Igl KO mouse model on the B6 strain background is specifically engineered to delete the λ light chain gene segments, allowing for focused study on the role of κ light chains in immune responses, autoimmune diseases, and immunoglobulin diversity. With its unique genetic profile, the B6-Igl KO mouse model provides invaluable insights for advancing antibody-based research and therapeutic discovery. Dive into the features and applications of this groundbreaking knockout mouse model, optimized for both preclinical and biomedical research in immunology.
Immunoglobulins (Ig) are large “Y”-shaped glycoprotein molecules which exhibit antibody activity or structures similar to antibodies which are used by the immune system to identify and neutralize antigens. Immunoglobulins are classified into two types: secreted (soluble) and membrane-bound forms (which contain a hydrophobic transmembrane region). Membrane-bound immunoglobulins (mIg) are part of the B-cell antigen receptor (BCR) complex on the B cell surface, primarily responsible for recognizing antigens and aiding in B cell activation and differentiation. Secreted immunoglobulins (sIg), also known as antibodies (Ab), are primarily found in serum and body fluids. These antibodies are produced by plasma cells (differentiated from B cells), and are capable of specific binding to antigens and mediating immune responses.
Structurally, Igs consist of two identical light chains and two identical heavy chains.[1-2] Mammals produce two types of light chains, kappa (κ) and lambda (λ), but individual B cells express only one kind. The newly introduced B6-Igl Knockout Mouse is a model that achieves knockout (KO) of the λ light chain to specifically express κ chain immunoglobulins.
Immunoglobulins (Ig) are composed of two identical light chains (L) and two identical heavy chains (H), forming a classic Y-shaped structure through interchain disulfide bonds and non-covalent interactions, with a flexible hinge region joining them.[3-4] Each heavy and light chain contains a variable region and a constant region, with the variable region responsible for recognizing and binding to specific antigens. Antibody diversity primarily arises from the sequence differences in these variable regions, enabling B cells to recognize countless different antigens. Although they are functionally similar, a single mammalian B cell can express only one type of light chain, either κ or λ. The κ-to-λ chain ratio varies across species. In humans, the κ-to-λ ratio is approximately 2:1; whereas in mice, this ratio is about 20:1, with most mouse B cells expressing the κ light chain.[5]
The variable region diversity is further enhanced through the immunoglobulin rearrangement process, also known as V(D)J recombination, where the genes that encode the B-cell receptor are rearranged to create unique immunoglobulins. The gene segments encoding antibodies (Ig gene loci) consist primarily of a variable region (V) and a constant region (C). The highly variable V region includes the variable (V) gene, diversity (D) gene, and joining (J) gene, which are linked through random DNA rearrangements and then joined with the relatively conserved constant (C) region to encode different types of antibodies.[6]
During B cell development, functional B cell receptors (BCRs) are generated through gene rearrangement. B cells preferentially rearrange the κ light chain gene, with the λ light chain (Igλ) serving as an alternative to the κ light chain (Igκ). This mechanism ensures that even if Igκ rearrangement fails, B cells can still produce functionally diverse antibodies, which is critical for maintaining the antibody repertoire.[8-10] As part of the BCR, Igλ can bind specific antigens, promoting B cell activation and differentiation into plasma and memory B cells. Abnormal rearrangement or dysfunction of Igλ expression can lead to autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, and is also associated with B cell malignancies like multiple myeloma and light chain amyloidosis (AL amyloidosis).[11-13] Furthermore,Igλ chain deletions or abnormalities are linked to conditions characterized by low immunoglobulin levels and increased susceptibility to infections. such as hypogammaglobulinemia, common variable immunodeficiency (CVID), and primary immunodeficiency diseases (PIDD).[14-16]
Both the λ light chain and κ light chain gene loci lack D genes and contain only V, J, and C gene segments. Cyagen has developed the B6-Igl KO Mouse (Product No.: C001550) by using gene-editing technology to knock out all gene sequences encoding the V, J, and C regions within the mouse λ light chain gene locus (Igl). As a result, this mouse model no longer expresses the λ light chain, with B cells specifically expressing only the κ light chain. Below are the details of this model.
Results indicate that in wild-type mice, B cells primarily express the κ light chain (Igκ), with a small subset of B cells expressing the λ light chain (Igλ). In contrast, due to the knockout of the λ light chain (Igl) gene locus in B6-Igl KO mice, B cells exclusively express the κ light chain (Igκ), with no λ light chain expression detected.
With the deletion of the λ light chain gene locus (Igl), B cells in B6-Igl KO mice (Product No.: C001550) express only κ light chain immunoglobulins. Therefore, this model can be used to generate mouse antibodies containing only the κ light chain, to study the role of the λ light chain in B cell development and function, and to analyze the mechanisms involving the λ light chain in specific immune responses or autoimmune diseases. This model offers potential for exploring antibody diversity, immune system regulation, and potential therapeutic approaches.
B6-Igl KO mice can be crossed with humanized light chain mouse models to develop mice that express human-specific light chains, enabling the generation of fully human antibodies for research and therapeutic development. Alternatively, other types or species-specific antibody sequences can be inserted into the mouse model for in vivo studies in cases where mouse antibody sequences are absent.
Cyagen has developed various genetic disease models, inducible disease models, target humanized models, and fully human antibody mouse models in the fields of immunology and human antibody research. These models provide researchers with powerful tools for developing targeted therapies and antibody drugs for various diseases.
| Product Number | Model Name | Strain Background | Applications |
|---|---|---|---|
| C001413 | B6-hCTLA4 | C57BL/6NCya | Development and screening of CTLA4-targeted inhibitors/antibody drugs; Evaluation of the efficacy and safety of CTLA4-targeted inhibitors/antibody drugs; Assessment of tumor immunotherapy and research on immune system mechanisms; Research on autoimmune diseases. |
| C001419 | B6-hCD47 | C57BL/6JCya | Development and screening of CD47-targeted inhibitors/antibody drugs; Evaluation of the efficacy and safety of CD47-targeted inhibitors/antibody drugs; Assessment of tumor immunotherapy and research on tumor immune evasion mechanisms. |
| C001420 | B6-hPDL1-V | C57BL/6NCya | PDL1 (aka CD274)-targeted drug development, screening, and evaluation of efficacy and safety; Assessment of tumor immunotherapy; Research on the immune system and tumor immune evasion mechanisms. |
| C001524 | hPD-1 | C57BL/6JCya | Immune checkpoints, tumor research. |
| C001272 | hF11 | C57BL/6NCya | Factor XI deficiency, Hemophilia C (Rosenthal syndrome); related to blood clotting disorders |
| C001400 | B6J-hANGPTL3 | C57BL/6JCya | Research on metabolic diseases such as atherosclerosis and hyperlipidemia; Studies on angiogenesis and endothelial cell adhesion; Development and screening of ANGPTL3-targeted drugs. |
| C001401 | B6-hIGHG1 | C57BL/6NCya | Research on the mechanisms and pathways of immunoglobulins; Studies on the development and screening of IgG antibody drugs; Research on tumor proliferation, migration, and chemotherapy resistance; Studies on diseases such as chronic lymphocytic leukemia and amyloidosis. |
| C001421 | B6-hGLP-1R | C57BL/6NCya | Research on the pathogenic mechanisms and drug development screening for obesity and type 2 diabetes; Study of other metabolic diseases such as cardiovascular and myocardial diseases; Research on neuroprotective effects in neurological diseases. |
| C001492 | B6-hALB (HSA) | C57BL/6NCya | Development and evaluation of ALB-targeted drugs; Design and evaluation of albumin-based drug carriers; Research on ALB-related metabolic diseases. |
| C001497 | B6-hCALCRL | C57BL/6JCya | Development of migraine treatment drugs, efficacy, and safety evaluation; Research on vascular biology and blood pressure regulation; Study of cell proliferation and apoptosis; Research on tumor growth inhibition and inflammation; Investigation of hematopoietic stem/progenitor cell generation and differentiation. |
| C001500 | B6-hFCGR1 | C57BL/6NCya | Research on antibody-dependent cell-mediated cytotoxicity (ADCC); Study of immune system phagocytosis and antigen presentation; Assessment of affinity, pharmacology, and efficacy of IgG antibody drugs based on FcγRI receptors. |
| C001523 | B6-hCALCA | C57BL/6JCya | Migraine drug development, efficacy, and safety evaluation; Vascular biology and blood pressure regulation research; Cell proliferation and apoptosis studies; Tumor growth inhibition and inflammation research; Hematopoietic stem/progenitor cell generation and differentiation research. |
| C001520 | B6-hGDF15 | C57BL/6JCya | Heart disease, diabetes, anorexia, colorectal cancer, prostate cancer, etc. |
| C001521 | B6-hLPA(CKI) | C57BL/6NCya | Arteriosclerosis, hyperlipidemia, thrombotic cardiovascular disease. |
| C001522 | B6-hLPA(CKI)/Alb-cre | C57BL/6NCya | Arteriosclerosis, hyperlipidemia, thrombotic cardiovascular disease. |
| C001325 | B6-hCD3 | C57BL/6NCya | Immunology Research; T Cell Activation and Antigen Recognition Research; Immunosuppressive Therapy Research for Autoimmune Diseases |
| C001326 | BALB/c-hCD3 | BALB/cAnCya | Immunology Research; T Cell Activation and Antigen Recognition Research; Immunosuppressive Therapy Research for Autoimmune Diseases |
| C001542 | H11-Alb-hLPA | C57BL/6NCya | Lp(a) cardiovascular disease, atherosclerosis, hyperlipidemia, thrombotic cardiovascular disease. |
| CR004 | SD-Rosa-hAGT | Sprague-Dawley | Hypertension drug screening model. |
| I001192 | H11-Alb-hHSD17B13 | C57BL/6JCya | Metabolic dysfunction-associated fatty liver disease (MAFLD), Metabolic dsfunction-asociated seatohepatitis (MASH). |
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