Somatic hypermutation in mouse λ chains

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Abstract
Summary: The frequency and distribution of somatic hypermutation in immunoglobulin genes and the effect of amino acid substitution on the structure/function of antibodies were studied using hybridomas that secrete anti‐(4‐hydroxy‐3‐nitrophenyl)acetyl (NP) monoclonal antibodies bearing Xl chains. A high frequency of mutation was observed in V‐J exons and J‐C introns of rearranged and active λ1 chains but not in the 5′‐non‐coding regions of these chains. Since a similar distribution was observed in inactive λ2 chain genes, 5′‐non‐coding regions containing a promoter were considered to be protected from mutation in view of their apparent importance. Using transgenic mice carrying chloramphenicol acetyl transferase transgenes driven by the VH promoter and heavy‐chain intron enhancer, it was also revealed that these cis‐acting elements are important in the induction of somatic hypermutation and are capable of inducing mutation even in non‐immunoglobulin genes.