Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgV(H) genes

Deborah K. Dunn-Walters, Ahmet Dogan, Laurent Boursier, Connie M. MacDonald, Jo Spencer

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Somatic hypermutation introduces mutations into IgV genes during affinity maturation of the B cell response. Mutations are introduced nonrandomly, and are generally targeted to the complementarity determining regions (CDRs). Subsequent selection against mutations that result in lower affinity or nonfunctional Ig increases the relative number of mutations in the CDRs. Investigation of somatic hypermutation is hampered by the effects of selection. We have avoided this by studying out-of-frame human IgV(H)4.21 and 251 genes, which, being unused alleles, are unselected. By comparison of the frequency of A, C, G, and T nucleotides at positions -3 to +3 around mutated or unmutated A, C, and G nucleotides, we have identified flanking sequences that most commonly surround mutated bases. Distinct trends in flanking sequences that were unique for each base were observed. Statistically significant trends that were common to both lgV(H)4.21 and 251 were used to deduce motifs that bias somatic hypermutation. The motifs deduced from this data, with targeted bases in regular type, are AANB, WDCH, and DGHD (where W = A/T, B = C/G/T, D = A/G/T, H = A/C/T, and N = any base). Mutations from C and G in two further groups of out-of-frame human IgV(H) genes, not used in the deduction of the motifs, occurred significantly within the motifs for C and G. The proposed target sequence for G is within the reverse complement of the target sequence for C, suggesting that the hypermutation mechanism may target only G or C. The mutation in the complementary base would appear on the other strand following replication.

Original languageEnglish (US)
Pages (from-to)2360-2364
Number of pages5
JournalJournal of Immunology
Volume160
Issue number5
StatePublished - Mar 1 1998
Externally publishedYes

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Mutation
Genes
Complementarity Determining Regions
Nucleotides
B-Lymphocytes
Alleles

ASJC Scopus subject areas

  • Immunology

Cite this

Dunn-Walters, D. K., Dogan, A., Boursier, L., MacDonald, C. M., & Spencer, J. (1998). Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgV(H) genes. Journal of Immunology, 160(5), 2360-2364.

Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgV(H) genes. / Dunn-Walters, Deborah K.; Dogan, Ahmet; Boursier, Laurent; MacDonald, Connie M.; Spencer, Jo.

In: Journal of Immunology, Vol. 160, No. 5, 01.03.1998, p. 2360-2364.

Research output: Contribution to journalArticle

Dunn-Walters, DK, Dogan, A, Boursier, L, MacDonald, CM & Spencer, J 1998, 'Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgV(H) genes', Journal of Immunology, vol. 160, no. 5, pp. 2360-2364.
Dunn-Walters DK, Dogan A, Boursier L, MacDonald CM, Spencer J. Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgV(H) genes. Journal of Immunology. 1998 Mar 1;160(5):2360-2364.
Dunn-Walters, Deborah K. ; Dogan, Ahmet ; Boursier, Laurent ; MacDonald, Connie M. ; Spencer, Jo. / Base-specific sequences that bias somatic hypermutation deduced by analysis of out-of-frame human IgV(H) genes. In: Journal of Immunology. 1998 ; Vol. 160, No. 5. pp. 2360-2364.
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