Distribution and Nucleotide Biases of the Somatic Hypermutations in the Functional Kappa Light Chain Gene of a Human Follicular Lymphoma Line

The immunoglobulin kappa chain gene of human lymphoma cell line HF-1.3.4 was partially sequenced from the 3′ end of the leader exon 2.0 kb downstream. The sequenced stretch of DNA included 1.5 kb of the non-coding JK region 3′ to the JK2 element of the mature gene. Among the known VK germline genes the closest relative was KV328, which was 91% homologous to HF-1.3.4. In the 1.5 kb JK region homology with JK allele of Whitehurst et al. (allele 2) was 89%, with the allele of Hieter et al. (allele 1) 87%. The vast majority of the differences located in the leader intron, the VJ exon or 0.6 kb 3′ to the exon, a localization characteristic of somatic hypermutations of immunoglobulin genes. Another indication that most of the differences observed were due to somatic hypermutations is that the 153 bp stretch of the kappa constant gene (CK) sequenced from the mRNA was 100% homologous with the published CK sequence. The most differences between the JK region sequence and that of Whitehurst et al. probably represent somatic mutations: 43% were transversions, 55% transitions and 2% deletions. In the non-coding JK region transversions of C.G to G.C rather than to A.T were heavily over-represented. This is possibly a feature of B-cell hypermutations in humans and mice.