Somatic hypermutation of Ig genes in patients with xeroderma pigmentosum (XP-D)

Abstract

Antibody diversification by somatic hypermutation occurs by the introduction of nucleotide substitutions in and around the rearranged Ig V gene segments. Several characteristics of the process suggest that the introduction of mutations is linked to Ig gene transcription. Since there is a connection between mutation and repair with indications that both processes might show linkage to transcription, we asked whether defects in a component of the transcription factor TFIIH which lead to an inability to carry out nucleotide excision repair also affect somatic hypermutation. A PCR strategy was devised that required small samples of peripheral blood and enabled us to monitor hypermutation of a single, abundantly used VH gene. However, the results showed that in xeroderma pigmentosum patients (complementation group D), somatic hypermutaton appears to take place unaffected as regard both extent and distribution.