Sequences of mouse immunoglobulin light chain genes before and after somatic changes

Abstract

We have determined the nucleotide sequences of the germ line gene as well as a corresponding somatically mutated and rearranged gene coding for a mouse immunoglobulin λ 1 type light chain. These sequencing studies were carried out on three Eco RI-DNA fragments which had been cloned from BALB/c mouse embryos or a λ 1 chainsecreting myeloma, H2020. The embryonic DNA clone Ig 99λ contains two protein-encoding segments, one for the majority of the hydrophobic leader (L) and the other for the rest of the leader and the variable (V) region of the λ 0 chain (Cohn et al., 1974); these segments are separated by a 93 base pair (bp) intervening sequence (I-small). The coding of the V region ends with His at residue 97. The second embryonic DNA clone Ig 25λ includes a 39 bp DNA segment (J) coding for the rest of the conventionally defined V region (that is, up to residue 110), and also contains the sequence coding for the constant (C) region approximately 1250 untranslated bp (l-large) away from the J sequence. The J sequence is directly linked with the V-coding sequence in the myeloma DNA clone, lg 303λ, which has the various DNA segments arranged in the following order: 5′ untranslated region, L, I-small, V linked with J, l-large, C, 3′ untranslated sequence. The Ig 303λ V DNA sequence codes for the V region synthesized by the H2020 myeloma and is different from the Ig 99λ V DNA sequence by only two bases. No silent base change was observed between the two DNA clones for the entire sequence spanning the 5′ untranslated regions and the V-coding segments. These results confirm the previously drawn conclusion that an active complete λ 1 gene arises by somatic recombination that takes place at the ends of the V-coding DNA segment and the J sequence. No sequence homology was observed at or near the sites of the recombination.