Distribution of t (14; 18)‐positive, putative lymphoma precursor cells among B‐cell subsets in healthy individuals 1

C Hirt, G Dölken, S Janz… - British journal of …, 2007 - Wiley Online Library
C Hirt, G Dölken, S Janz, CS Rabkin
British journal of haematology, 2007Wiley Online Library
Summary 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 …
Summary
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: 380/106) than in antigen‐naïve (median: 16/106) or switched memory (median: 5/106) 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.
Wiley Online Library