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Structural alterations in J regions of mouse immunoglobulin λ genes are associated with differential gene expression

Abstract

Immunoglobulin λ light chains in the mouse comprise three types: λ1, λ2 and λ3 (refs 1–3 respectively) and are encoded by three constant region (Cλ) and two variable region (Vλ) genes. The Cλ2 and Cλ3 protein sequences differ at only 5 amino acid positions whereas Cλ1 differs from both by about 30 amino acids. The Cλ1 and Cλ3 genes are closely linked4, separated by 3 kilobases (kb) of DNA. The Cλ2 gene is closely linked to a Cλ4 gene, but is an unknown distance from the Cλ3–Cλ1 cluster4,5. Although the Cλ4 gene shares homology with Cλ1, we show here that it represents a pseudogene. Only two germ-line V genes appear to be expressed in mouse λ chains: Vλ1 is used in association with either Cλ1 (ref. 1) or Cλ3 (ref. 6), while Vλ2 has only been found with Cλ2 (ref. 2). Differential gene expression is observed in the λ locus. Among mouse serum antibodies, λ1 chains occur 10 times more frequently than λ2 (ref. 7) or λ3 (ref. 3) chains while λ4 chains have not been identified. We have now searched for structural differences between Cλ genes which could explain this differential expression. Our nucleotide sequence analysis indicates that Cλ4 is not expressed due to an inactive RNA splice site. Although no structural defects were found in Cλ2 or Cλ3, substitutions in the rearrangement recognition sequences associated with Jλ2 and Jλ3 segments, together with nearby competing pseudo recognition sequences, may explain the relatively low levels of Cλ2 and Cλ3 gene expression.

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Miller, J., Selsing, E. & Storb, U. Structural alterations in J regions of mouse immunoglobulin λ genes are associated with differential gene expression. Nature 295, 428–430 (1982). https://doi.org/10.1038/295428a0

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