Clonal diversity, somatic mutation, and immune memory to phosphocholine-keyhole limpet hemocyanin

Group II antibodies to phosphocholine (PC)-keyhole limpet hemocyanin in BALB/c mice are genetically diverse and of a defined binding phenotype which recognizes the hapten, phenyl-PC, and PC coupled to protein but not free PC. We sequenced the V regions of 14 κ and λ-bearing group II antibodies. Both types show extensive somatic mutations. The pattern of the mutations differs between κ and λ antibodies. The nature of the somatic mutation in λ chains suggests strong Ag selection on the L chain but not the H chain of the λ-bearing antibodies. The reverse pattern of selection was observed among κ-containing antibodies wherein the accumulation of replacement mutations in the CDR of the H chain appears to result from selection while changes in the L chain appear unselected. From these findings it appears that somatic mutation plays a major role in anti-PC-keyhole limpet hemocyanin memory development because all 14 antibodies displayed changes from germ-line sequences.