J. Exp. Med., Volume 188, Number 9, November 2, 1998 1679-1689

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

By Ulf Klein, Klaus Rajewsky, and Ralf Küppers

From the Institute for Genetics, University of Cologne, 50931 Cologne, Germany

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 ~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 ~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 genes. This might be due to an intrinsically lower mutation rate in  light chain genes compared with heavy chain genes and/or result from  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.

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• Malbran, A., Belmonte, L., Ruibal-Ares, B., Bare, P., Massud, I., Parodi, C., Felippo, M., Hodinka, R., Haines, K., Nichols, K. E., de Bracco, M. M. (2004). Loss of circulating CD27+ memory B cells and CCR4+ T cells occurring in association with elevated EBV loads in XLP patients surviving primary EBV infection. Blood 103: 1625-1631 [Abstract] [Full Text]  
• Wagner, M., Poeck, H., Jahrsdoerfer, B., Rothenfusser, S., Prell, D., Bohle, B., Tuma, E., Giese, T., Ellwart, J. W., Endres, S., Hartmann, G. (2004). IL-12p70-Dependent Th1 Induction by Human B Cells Requires Combined Activation with CD40 Ligand and CpG DNA. J. Immunol. 172: 954-963 [Abstract] [Full Text]  
• Novak, A. J., Darce, J. R., Arendt, B. K., Harder, B., Henderson, K., Kindsvogel, W., Gross, J. A., Greipp, P. R., Jelinek, D. F. (2004). Expression of BCMA, TACI, and BAFF-R in multiple myeloma: a mechanism for growth and survival. Blood 103: 689-694 [Abstract] [Full Text]  
• Basso, K., Liso, A., Tiacci, E., Benedetti, R., Pulsoni, A., Foa, R., Di Raimondo, F., Ambrosetti, A., Califano, A., Klein, U., Favera, R. D., Falini, B. (2004). Gene Expression Profiling of Hairy Cell Leukemia Reveals a Phenotype Related to Memory B Cells with Altered Expression of Chemokine and Adhesion Receptors. J. Exp. Med. 199: 59-68 [Abstract] [Full Text]  
• Song, H., Cerny, J. (2003). Functional Heterogeneity of Marginal Zone B Cells Revealed by Their Ability to Generate Both Early Antibody-forming Cells and Germinal Centers with Hypermutation and Memory in Response to a T-dependent Antigen. J. Exp. Med. 198: 1923-1935 [Abstract] [Full Text]  

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