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Immunity. 1998 Dec;9(6):859-69.

TdT-accessible breaks are scattered over the immunoglobulin V domain in a constitutively hypermutating B cell line.

Author information

1
Medical Research Council Laboratory of Molecular Biology, Cambridge, United Kingdom.

Abstract

Searching for an in vitro model for somatic hypermutation, we have identified an IgM-expressing Burkitt lymphoma line that constitutively diversifies its immunoglobulin V domain at high rate during culture. As in in vivo, the mutations are largely nucleotide substitutions with the pattern of substitutions revealing a component of the human hypermutation program that is preferentially targeted to G/C residues. The substitutions frequently create stop codons with IgM-loss variants also being generated by V domain-specific deletions and duplications. However, in transfectants expressing terminal deoxynucleotidyl transferase, many IgM-loss variants additionally arise through short nontemplated nucleotide insertions into the V (but not C) domain. Thus, antibody hypermutation is likely accompanied by DNA strand breaks scattered within the mutation domain.

PMID:
9881976
DOI:
10.1016/s1074-7613(00)80651-2
[Indexed for MEDLINE]
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