High frequency of somatically mutated IgM molecules in the human adult blood B cell repertoire

Nucleotide sequence analysis of cDNA encoded by the single member of the human immunoglobulin VH6 gene family show that blood B cells in adults, but not in neonates, frequently express somatically mutated IgM molecules. The number of mutations in VH6-encoded cDNA from adult blood ranged from 2 to 19 mutations/VH gene (average 10.1/VH gene). The distribution of silent and replacement mutations suggests that at least some of the VH6 genes were derived from B cells that were activated and selected by antigen. We conclude that the blood B cell repertoire in adult humans, in contrast to its much-studied murine splenic counterpart, is a rich source of highly mutated IgM molecules.