Although the reported diversity of germline light chain gene allelic variants is limited, with only a few IGKV and IGLV genes together shaping the expressed light chain repertoire, an important function of the light chain is to prevent self-response and plays a specific role in the autoimmune response. As a pioneer in immunomics research, CD Genomics offers the light chain of BCR sequencing services.
The bonded structure of immunoglobulin (Ig) consists of four polypeptide chains, two identical pairs of copies of the heavy (H) and light (L) chains, the latter being named kappa (κ) or lambda (λ) chains. The κ gene fragment is encoded on chromosome 2 and includes 52 V genes and 5 J genes, whereas the λ gene fragment is encoded on chromosome 22 and includes 30 V genes and 7 J genes.
Fig.1 The gene structure of BCR. (Guevara-Hoyer, K., et al., 2020)
The L chain is incorporated into the Ig molecule during B-cell development. In small pre-B cells, the L chains (κ and λ) undergo recombination. When this leads to effective recombination of the L chain, it is expressed together with μHC to form a BCR on the surface of pre-B cells. Excess L-chains are produced throughout B-cell development up to plasma cells, where they bind to H chains and excess L chains enter the bloodstream as free L chains (FLCs), which reflects B-cell activation.
Fig.2 Scheme of the B cell maturation and differentiation. (Guevara-Hoyer, K., et al., 2020)
There are several different types of immunoglobulin H chains synthesized by B cells, but mature B cells can express only one immunoglobulin L chain, κ or λ. κ rearrangements usually precede λ rearrangements and there are more κ antibodies in human peripheral blood, with κ/λ ratios reported to be between approximately 1.5 and 2. However, in antigen-selected populations, this ratio can vary considerably depending on the class of antibody H chain.
Extensive phenotypic differences, such as conformational flexibility, half-life, and the tendency to alter antibody specificity, have been noted between antibodies bearing κ or λ L chains. Alterations in the κ:λ ratio have also been reported to characterize certain diseases. Sequencing of BCR L chains to investigate potential differences between κ and λ antigen binding sites will facilitate our understanding of the immune response and subsequent clinical diagnostic applications.
L chain is one of the important components of the BCR repertoire. However, the L chain library is restricted compared to the H chain. Numerous studies have shown that an important factor limiting the library is the need for L chain rearrangements to minimize BCR self-reactivity. In addition, the L chain κ/λ ratio assay has important diagnostic value for a variety of cancers and infectious diseases.
CD Genomics provides light chain sequencing and analysis services to advance basic research on autoimmune responses and κ/λ ratio-based diagnostic applications. In addition, with our professional bioinformatics team, we provide reliable data processing and analysis services to promote the projects of our clients.
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Multiple Library Construction Methods. |
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Advanced High-throughput Sequencing Platform. |
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Professional Data Analysis Team. |
CD Genomics has been diving into immunomics research for many years and has deep collaborations with several research institutions and companies around the world. Based on the advanced technology of high-throughput sequencing, we sequence and analyze the BCR repertoire to provide important data support for the study of the immune response. Please contact us for more information.