Evidence for a large compartment of IgM-expressing memory B cells in humans.
The recent finding of somatically mutated mu heavy chain transcripts in human peripheral blood (PB) B lymphocytes suggests that T-dependent B-cell memory might not be restricted to class-switched cells. We provide here evidence that IgM-only PB B cells are likely to be the IgM-expressing counterpart of classical (IgM- IgD-) memory B cells in humans. As shown by molecular single cell analysis, most IgM-only cells carry mutated V region genes, like class-switched cells. Although both subsets represent populations of nonactivated, resting cells, they express higher levels of Ig mRNA than naive (IgM+ IgD+) B cells. IgM-only and class-switched cells are CD38- CD77-, and mostly CD23-, thus neither resembling germinal center nor naive B cells. Because many IgM-expressing B cells located in secondary lymphoid tissues resemble IgM-only PB B cells in terms of cell phenotype, we propose that the human lymphoid system contains a large compartment of IgM-expressing memory cells. Moreover, these cells seem to represent the nonmalignant counterparts of IgM-expressing tumor cells in sporadic Burkitt's lymphoma, MALT lymphoma, monocytoid B-cell lymphoma, and diffuse large-cell lymphoma that were found to harbor somatically mutated V genes.
Klein
U
U
Institute for Genetics, University of Cologne, Germany.
Küppers
R
R
Rajewsky
K
K
D016175:B-Lymphocyte Subsets / Q000276:immunology*; D018076:DNA, Complementary / Q000235:genetics; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000235:genetics / Q000276:immunology; D007075:Immunoglobulin M / Q000235:genetics / Q000276:immunology*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007156:Immunologic Memory; D008221:Lymphoid Tissue / Q000276:immunology; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000473:pathology; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction
D018076:DNA, Complementary; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region