Faculty Collaboration Database

Distribution of t(14;18)-positive, putative lymphoma precursor cells among B-cell subsets in healthy individuals. Br J Haematol 2007 Aug;138(3):349-53

Date

07/07/2007

Pubmed ID

17614821

DOI

10.1111/j.1365-2141.2007.06671.x

Scopus ID

2-s2.0-34447133546 (requires institutional sign-in at Scopus site)   34 Citations

Abstract

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.

Author List

Hirt C, Dölken G, Janz S, Rabkin CS

Author

Siegfried Janz MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

B-Lymphocyte Subsets
Chromosomes, Human, Pair 14
Chromosomes, Human, Pair 18
Clone Cells
Gene Frequency
Gene Rearrangement, B-Lymphocyte
Genes, Immunoglobulin
Genes, bcl-2
Humans
Immunologic Memory
Immunophenotyping
Lymphoma, Non-Hodgkin
Polymerase Chain Reaction
Translocation, Genetic