Somatic hypermutation in the heavy chain locus correlates with transcription.
Three mutant immunoglobulin heavy chain (IgH) insertion mice were generated in which a targeted nonfunctional IgH passenger transgene was either devoid of promoter (pdelta) or was placed under the transcriptional control of either its own RNA polymerase II-dependent IgH promoter (pII) or a RNA polymerase I-dependent promoter (pI). While the transgene mutation-frequency (0.85%) in memory B cells of pI mice was reduced compared to that in pII mice (1.4%), the distribution and the base exchange pattern of point mutations were comparable. In pdelta mice, the mutation frequency was drastically reduced (0.09%). The mutation frequencies correlated with the levels of transgene-specific pre-mRNA expressed in germinal center B cells isolated from the mutant mice.
Institute for Genetics, University of Cologne, Germany.
Y
Y
Fukita
H
H
Jacobs
K
K
Rajewsky
D000818:Animals; D005260:Female; D018858:Germinal Center; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009154:Mutation; D011061:Poly A; D011401:Promoter Regions, Genetic; D012318:RNA Polymerase I / Q000235:genetics; D012319:RNA Polymerase II / Q000235:genetics; D012322:RNA Precursors; D014158:Transcription, Genetic
D007143:Immunoglobulin Heavy Chains; D012322:RNA Precursors; D011061:Poly A; D012319:RNA Polymerase II; D012318:RNA Polymerase I