An unbalanced translocation involving chromosome 14 is the probable cause for loss of potentially functional rearranged immunoglobulin heavy chain genes in the Epstein-Barr virus-positive Hodgkin's lymphoma-derived cell line L591.
In the vast majority of cases, Hodgkin-Reed Sternberg (H-RS) cells, the malignant cells in Hodgkin's lymphoma (HL), are derived from germinal centre B cells. In some cases, somatic mutations within the rearranged immunoglobulin heavy (IgH) chain genes were detected, rendering potentially functional gene rearrangements non-functional. In these H-RS cells the expression of high-affinity B-cell receptors (BCR) was prevented. As in other cases only one non-productive IgH chain gene rearrangement was amplified from H-RS cells, it was speculated whether, in these cases, the functionally rearranged IgH chain genes were lost. An alternative explanation might be that the rearranged genes could not be amplified owing to a high load of somatic mutations within the primer binding sites. Here, we showed that, in the HL-derived Epstein-Barr virus (EBV)-positive cell line L591, only one non-functional somatically mutated IgH gene rearrangement could be detected. The other potentially functional IgH gene rearrangement was lost as a result of an unbalanced translocation affecting the long arm of chromosome 14. Moreover, L591 cells express the EBV latent membrane proteins LMP1 and LMP2A, which might have contributed to the 'escape' of these cells from apoptosis within the germinal centre. We conclude that, apart from the introduction of 'crippling mutations' into the rearranged VDJ genes rearrangement, deletions of the IGH locus may be regarded as another mechanism to prevent the expression of a BCR in H-RS cells.
Vockerodt
Martina
M
Department of Internal Medicine I, Universitity of Cologne, Cologne, Germany. Martina.Vockerodt@medizin.uni-koeln.de
Belge
Gazanfer
G
Kube
Dieter
D
Irsch
Johannes
J
Siebert
Reiner
R
Tesch
Hans
H
Diehl
Volker
V
Wolf
Jürgen
J
Bullerdiek
Jörn
J
Staratschek-Jox
Andrea
A
D000595:Amino Acid Sequence; D002051:Burkitt Lymphoma / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006801:Humans; D017421:Sequence Analysis; D014178:Translocation, Genetic / Q000235:genetics*; D014407:Tumor Cells, Cultured