A new memory CD27-IgG+ B cell population in peripheral blood expressing VH genes with low frequency of somatic mutation

In humans, up to 40% of peripheral B cells express CD27 and have hypermutated variable regions in their Ig genes. The CD27(+) B cells are considered to be derived from germinal center following specific antigenic stimulation. Actually, somatic hypermutation in Ig genes and CD27 expression are hallmarks of memory B cells. However, the blood IgM(+)IgD(+)CD27(+) B cells were recently associated to splenic marginal zone B cells and proposed to be a subset distinct from germinal center-derived memory B cells showing premutated Igs. The results presented herein further weaken this bona fide association because B cells expressing surface IgG, but not CD27, were found in human blood. Representing 1-4% of all peripheral B cells and similar to 25% of the IgG(+) blood B cells, this population expressed mutated IgG genes showing antigenic selection characteristics but with lower mutation frequencies than that of CD27(+)IgG(+) B cells. However, their morphology and phenotype were similar to that of CD27(+)IgG(+) cells. Interestingly, the proportion of IgG2 over IgG3 transcripts was opposite in CD27(-)IgG(+) and CD27(+)IgG(+) cells, suggesting distinct functions or origins. Overall, these findings extend the memory B cell reservoir beyond the CD27(+) compartment and could provide further insights into B cell disorders of unknown etiology.