An immunoglobulin promoter region is unaltered by DNA rearrangement and somatic mutation during B-cell development

Abstract

The V1 gene encodes the heavy chain variable region of antibodies that bind to phosphorylcholine in the Balb/c mouse. V1 genes have been cloned from mouse sperm DNA, an IgM-producing tumor HPCM2 and an IgA-producing tumor M167. The transcription start site of the V1 gene has been mapped 63 +/- 1 base pairs from the coding sequence for both alpha and mu transcripts. Comparison of flanking DNA sequence 574 base pairs 5' to the V1 transcription start site in sperm, HPCM2 and M167 DNA reveals that sperm and HPCM2 sequences are completely identical in this region and the M167 sequence differs from them by a single base change. Although the coding region of the V1 gene has undergone a high (4%) rate of somatic mutation in M167 we demonstrate that the somatic mutation mechanism stops near the transcription start site. These results demonstrate that initiation of V1 gene transcription remains unchanged with respect to location and 5' sequences throughout B-cell development.