EVIDENCE FOR A LARGE COMPARTMENT OF IGM-EXPRESSING MEMORY B-CELLS IN HUMANS

The recent finding of somatically mutated mu heavy chain transcripts i n human peripheral blood (PB) B lymphocytes suggests that T-dependent B-cell memory might not be restricted to class-switched cells. We prov ide here evidence that IgM-only PB B cells are likely to be the IgM-ex pressing counterpart of classical (IgM(-)IgD(-)) memory B cells in hum ans. As shown by molecular single cell analysis, most IgM-only cells c arry mutated V region genes, like class-switched cells. Although both subsets represent populations of nonactivated, resting cells, they exp ress higher levels of Ig mRNA than naive (IgM(+)IgD(+)) B cells. IgM-o nly and class-switched cells are CD38(-)CD77(-), and mostly CD23(-), t hus 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 h uman lymphoid system contains a large compartment of IgM-expressing me mory cells. Moreover, these cells seem to represent the nonmalignant c ounterparts of IgM-expressing tumor cells in sporadic Burkitt's lympho ma, MALT lymphoma, monocytoid B-cell lymphoma, and diffuse large-cell lymphoma that were found to harbor somatically mutated V genes. (C) 19 97 by The American Society of Hematology.