HUMAN IGM+IGD+ B-CELLS, THE MAJOR B-CELL SUBSET IN THE PERIPHERAL-BLOOD, EXPRESS-V(CHI)-GENES WITH NO OR LITTLE SOMATIC MUTATION THROUGHOUT LIFE

Peripheral blood B cells of a 67-year-old person were separated into IgM+IgD+, IgM+IgD-, and IgM-IgD- subsets, and nucleotide sequences of expressed immunoglobulin light chain variable (V) regions encoded by V(kappa)3 and V(kappa)4 gene family members were determined from amplified cDNA. V region sequences from IgM+IgD+ cells (the major B cell population in the blood) showed no or little somatic mutation (0.3%), in contrast to V(kappa) sequences from IgM+IgD- and IgM-IgD- B cells (2.0% and 3.9%, respectively).This suggests that in the human like in the mouse, and independently of age, somatically mutated memory B cells accumulate in the compartment of IgM-IgD- cells, whereas the IgM+IgD+ subpopulation consists of cells whose antibody repertoire is mainly determined by V region gene rearrangements and N-region insertion, at the molecular level. The somatically mutated IgM+IgD- cells may represent early descendants of IgM+IgD+ cells recruited into the memory cell compartment.