Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express Vϰ genes with no or little somatic mutation throughout life

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Abstract
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 Vϰ3 and Vϰ4 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 Vϰ 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.