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 V(H)6 gene family show that blood B cells in adults, but not in neonates, frequently express somatically mutated IgM molecules. The number of mutations in V(H)6-encoded cDNA from adult blood ranged from 2 to 19 mutations/V(H) gene (average 10.1/V(H) gene). The distribution of silent and replacement mutations suggests that at least some of the V(H)6 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.