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Somatic mutation and antibody diversity
Nucleotide insertions or deletions determine novel amino acid sequences at the VH-D and D-JH junction sites. Since these cannot be predicted by known coding genes, they are regarded as a form of somatic mutagenesis. A second type of somatic mutation in Ig structural genes are the stochastic base substitutions that have now been found in both V region coding sequences and noncoding flanking sequences. It has been proposed that this form of mutagenesis may be related to the gene rearrangement process as well. A third type of mutagenesis has been associated with Ig CH switching. In this case, a higher frequency of substitutions has been observed in VH regions associated with C gamma and C alpha. A mechanism for the origin of this phenomenon is not known. An unexpectedly high rate of mutagenesis affecting Ig V genes has been observed to occur spontaneously in vitro.
Nucleotide insertions or deletions determine novel amino acid sequences at the VH-D and D-JH junction sites. Since these cannot be predicted by known coding genes, they are regarded as a form of somatic mutagenesis. A second type of somatic mutation in Ig structural genes are the stochastic base substitutions that have now been found in both V region coding sequences and noncoding flanking sequences. It has been proposed that this form of mutagenesis may be related to the gene rearrangement process as well. A third type of mutagenesis has been associated with Ig CH switching. In this case, a higher frequency of substitutions has been observed in VH regions associated with C gamma and C alpha. A mechanism for the origin of this phenomenon is not known. An unexpectedly high rate of mutagenesis affecting Ig V genes has been observed to occur spontaneously in vitro.