Tuning somatic hypermutation by transcription.
The dependence of somatic hypermutation on transcription was studied in three mutant immunoglobulin heavy chain (IgH) insertion mice in which a targeted non-functional VHB1-8 passenger transgene was either placed under the transcriptional control of a truncated DQ52 promoter (p delta), its own RNA polymerase II dependent IgH promoter (pII) or a RNA polymerase I dependent promoter (pI). The relative mutation-frequency of the VHB1-8 passenger transgene in memory B cells of p delta, pI and pII mice (7%, 60% and 100%) correlated with the relative levels of transgene-specific pre-mRNA expressed in germinal center B cells isolated from the mutant mice (8%, 72% and 100%, respectively). These data indicate that the mutation load of rearranged Ig genes can be tuned by transcription. The question, whether somatic hypermutation requires transcription per se or a specific component of the RNA polymerase II complex, is under investigation.
Basel Institute for Immunology, Switzerland.
H
H
Jacobs
A
A
Puglisi
K
K
Rajewsky
Y
Y
Fukita
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D005803:Genes, Immunoglobulin; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D014158:Transcription, Genetic
D017931:DNA Primers; D012319:RNA Polymerase II; D012318:RNA Polymerase I