Human immunoglobulin (Ig)M+IgD+ peripheral blood B cells expressing the CD27 cell surface antigen carry somatically mutated variable region genes:: CD27 as a general marker for somatically mutated (memory) B cells

Immunoglobulin (Ig)M(+)IgD(+) B cells are generally assumed to represent antigen-inexperienced, naive B cells expressing variable (V) region genes without somatic mutations. We report here that human IgM(+)IgD(+) peripheral blood (PB) B cells expressing the CD27 cell surface antigen carry mutated V genes, in contrast to CD27-negative IgM(+)IgD(+) B cells. IgM(+)IgD(+)CD27(+) B cells resemble class-switched and IgM-only memory cells in terms of cell phenotype, and comprise similar to 15% of PB B lymphocytes in healthy adults. Moreover, a very small population (<1% of PB B cells) of highly mutated IgD-only B cells was detected, which likely represent the PB counterpart of IgD-only tonsillar germinal center and plasma cells. Overall, the B cell pool in the PB of adults consists of similar to 40% mutated memory B cells and 60% unmutated, naive IgD(+)CD27(-) B cells (including CD5(+) B cells). In the somatically mutated B cells, V-H region genes carry a two- to threefold higher load of somatic mutation than rearranged V-kappa genes. This might be due to an intrinsically lower mutation rate in kappa light chain genes compared with heavy chain genes and/or result from kappa light chain gene rearrangements in GC B cells. A common feature of the somatically mutated B cell subsets is the expression of the CD27 cell surface antigen which therefore may represent a general marker for memory B cells in humans.