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 κ genes. This might be due to an intrinsically lower mutation rate in κ light chain genes compared with heavy chain genes and/or result from κ 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. B cell CD27 immunoglobulin D memory B cell somatic hypermutation Footnotes We are most grateful to Michaela Fahrig for excellent technical assistance and Alexander Scheffold for providing FITC-conjugated liposomes. We thank Christoph Göttlinger for help with the FACS ® , Julia Jesdinsky for sequencing work, and Andreas Thiel for discussions. Abbreviations used in this paper: FR framework region GC germinal center(s) PB peripheral blood R/S ratio of replacement to silent mutations Submitted: 1 July 1998 Revision received 13 August 1998
The Journal of Experimental Medicine – Rockefeller University Press
Published: Nov 2, 1998
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