Distribution of t(14;18)-positive, putative lymphoma precursor cells among B-cell subsets in healthy individuals

The t(14;18)(q32;q21) is the characteristic chromosomal translocation of follicular lymphoma (FL). Highly sensitive polymerase chain reaction (PCR) techniques can also detect t(14;18)-sequences in the blood and lymphoid tissues of healthy individuals (HI). The aim of this study was to determine the immunophenotypic markers of t(14;18)-positive cells in HI and to relate these features to lymphocyte maturation. B cells from 10 subjects with t(14;18)-positive and three subjects with t(14;18)-negative peripheral blood mononuclear cells (PBMC) were fluorescence-activated cell sorted for antigen-naïve (CD27(-)), immunoglobulin M (IgM) memory (IgM(+)CD27(+)) and switched memory (IgM(-) CD27(+)) cells. t(14;18)-recombinations were detected by quantitative PCR. Among PBMC-positive subjects, t(14;18)-frequency was significantly higher in IgM memory (median: 380/10(6)) than in antigen-naïve (median: 16/10(6)) or switched memory (median: 5/10(6)) B cells. All PBMC-negative subjects nevertheless had detectable t(14;18) in sorted B cells; levels were lower than in PBMC-positive subjects, but had the same relative predominance. These results suggest that t(14;18) is generated during early B-cell development in the bone marrow and that affected cells may mature and expand in germinal centres. t(14;18)-frequency was highest in IgM memory cells, a B-cell subset that shares immunophenotypic similarities with FL. The significance of these cells as lymphoma precursors or indicators of lymphoma risk remains to be established.