B6-Igl KO Mice

Catalog Number: C001550

Strain Name: C57BL/6NCya-Iglem1/Cya

Genetic Background: C57BL/6NCya

Reproduction: Homozygote × Homozygote

 

Strain Description

Antibodies, or immunoglobulins (Igs), are crucial components of the immune system, specifically recognizing and neutralizing foreign pathogens. They bind selectively to antigens, triggering an immune response. Upon antigen entry, B cells differentiate into plasma cells, which subsequently synthesize and secrete antibodies. Beyond neutralization, antibodies engage Fc receptors on T cells, macrophages, mast cells, and complement components, thereby facilitating antigen clearance through antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), or modulating the activation of classical pathways [1,2]. The immunoglobulin (Ig) structure comprises two identical light chains (L) and two identical heavy chains (H), forming a classical Y-shaped structure stabilized by interchain disulfide bonds, noncovalent interactions, and hinge regions [2,3]. Each heavy and light chain contains a variable region and a constant region; the variable regions are essential for recognizing and binding specific antigens. Antibody diversity arises largely from sequence variations within these variable regions, enabling B cells to detect a vast array of antigens. In mammals, immunoglobulins contain both kappa (κ) and lambda (λ) light chains. Although there are no significant functional differences between these two light chain types, individual B cells express only one type. The ratio of κ- to λ-expressing B cells varies by species: in humans, this ratio is approximately 2:1, whereas in mice, it is about 20:1, with the majority of mouse B cells expressing only κ light chains [4]. The gene segments encoding antibody structures (Ig motifs) are spatially separated in embryonic cells, predominantly comprising variable (V) and constant (C) regions. The highly variable V region includes variable (V), diversity (D), and joining (J) genes, which undergo random DNA rearrangements to connect with the relatively conserved C region, thereby encoding diverse antibody types [5]. Notably, antibody light chains lack D genes and are composed solely of V, J, and C gene fragments.

The B6-Igl KO mouse is a knockout model targeting the gene segment encoding the λ light chain. Through gene editing, the sequences encoding the V, J, and C regions of the mouse λ light chain (Igl) locus are completely ablated, resulting in the absence of B cells expressing immunoglobulin light chain λ. Consequently, B6-Igl KO mice serve as a valuable tool for investigating B cell development and function, generating κ light chain-only mouse antibodies, elucidating the role of the λ light chain in specific immune responses or autoimmune diseases, and exploring antibody diversity, immune regulatory mechanisms, and potential therapeutic strategies [6].


Strain Strategy

The gene segments encoding the λ chain (V+J+C) of the mouse antibody were completely knocked out using gene-editing technology.


Application

  • Investigation of B cell development and function, as well as the analysis of the role of the λ light chain in specific immune responses or autoimmune diseases.
  • Exploration of antibody diversity, immune system regulation mechanisms, and potential therapeutic strategies.

Validation Data

1. Proportion of B cells expressing different types of immunoglobulin (Ig) light chains


Figure 1. Proportion of B cells expressing immunoglobulin λ light chain (Igλ) and κ light chain (Igκ) in the spleen and bone marrow of wild-type (WT) and B6-Igl KO mice. The results indicate that B cells in WT mice predominantly express the κ light chain (Igκ), with a small proportion expressing the λ light chain (Igλ). In contrast, B6-Igl KO mice, due to the knockout of the λ light chain (Igl) gene locus, no longer express the Igλ light chain, with only the Igκ light chain being present.

 


References

[1] Sun Y, Huang T, Hammarström L, Zhao Y. The Immunoglobulins: New Insights, Implications, and Applications. Annu Rev Anim Biosci. 2020 Feb 15;8:145-169.
[2] Wilson IA, Stanfield RL. 50 Years of structural immunology. J Biol Chem. 2021 Jan-Jun;296:100745.
[3] Schroeder HW Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010 Feb;125(2 Suppl 2):S41-52.
[4] Larijani M, Chen S, Cunningham LA, Volpe JM, Cowell LG, Lewis SM, Wu GE. The recombination difference between mouse kappa and lambda segments is mediated by a pair-wise regulation mechanism. Mol Immunol. 2006 Mar;43(7):870-81.
[5] Giudicelli V, Chaume D, Lefranc MP. IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res. 2005 Jan 1;33(Database issue):D256-61.
[6] Zou X, Piper TA, Smith JA, Allen ND, Xian J, Brüggemann M. Block in development at the pre-B-II to immature B cell stage in mice without Ig kappa and Ig lambda light chain. J Immunol. 2003 Feb 1;170(3):1354-61