Somatic hypermutation in the heavy chain locus correlates with transcription

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Abstract

Three mutant immunoglobulin heavy chain (IgH) insertion mice were generated in which a targeted nonfunctional IgH passenger transgene was either devoid of promoter (pΔ) 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 pl mice was reduced compared to that in pll mice (1.4%), the distribution and the base exchange pattern of point mutations were comparable. In pΔ 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.

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Fukita, Y., Jacobs, H., & Rajewsky, K. (1998). Somatic hypermutation in the heavy chain locus correlates with transcription. Immunity, 9(1), 105–114. https://doi.org/10.1016/S1074-7613(00)80592-0

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