SOMATIC HYPERMUTATION IN THE HEAVY-CHAIN LOCUS CORRELATES WITH TRANSCRIPTION

Three mutant immunoglobulin heavy chain (IgH) insertion mice were gene rated in which a targeted nonfunctional IgH passenger transgene was ei ther devoid of promoter (p Delta) or was placed under the transcriptio nal control of either its own RNA polymerase II-dependent IgH promoter (pII) or a RNA polymerase I-dependent promoter (pI). While the transg ene mutation-frequency (0.85%) in memory B cells of pI mice was reduce d compared to that in pII mice (1.4%), the distribution and the base e xchange pattern of point mutations were comparable. In p Delta mice, t he mutation frequency was drastically reduced (0.09%). The mutation fr equencies correlated with the levels of transgene-specific pre-mRNA ex pressed in germinal center B cells isolated from the mutant mice.