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© The Rockefeller University Press, 0022-1007/1998/11/1679/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 9, November 2, 1998 1679-1689

Articles

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

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, VH 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.

Key Words: B cell • CD27 • immunoglobulin D • memory B cell • somatic hypermutation

Address correspondence to Ralf Küppers, University of Cologne, University Hospital, LFI E4 R706, Joseph-Stelzmannstr. 9, 50931 Cologne, Germany. Phone: 49-221-478-4490; Fax: 49-221-478-6383; E-mail: rkuppers{at}mac.genetik.uni-koeln.de

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: FR, framework region; GC, germinal center(s); PB, peripheral blood; R/S, ratio of replacement to silent mutations.


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