Identification of common germinal-center B-cell precursors in two patients with both Hodgkin's disease and non-Hodgkin's lymphoma.
BACKGROUND
Hodgkin's disease and non-Hodgkin's B-cell lymphoma occasionally occur in the same patient. The identification of a common precursor of the two types of lymphoma would show definitively that Reed-Sternberg cells originate from B cells.


METHODS
We studied lymphomas from two patients, one with a composite lymphoma (classic Hodgkin's disease and a follicular lymphoma in the same lymph node) and the other with a T-cell-rich B-cell lymphoma that was followed by classic Hodgkin's disease. Single Reed-Sternberg cells and non-Hodgkin's lymphoma cells from frozen sections were micromanipulated. The rearranged immunoglobulin variable-region genes (V genes) of the heavy and light chains were amplified by the polymerase chain reaction from genomic DNA and sequenced.


RESULTS
In both patients, the Reed-Sternberg cells were related clonally to the non-Hodgkin's lymphoma B cells. The V genes carried somatic mutations (a hallmark of germinal-center B cells and their descendants). In both patients, some somatic mutations were shared by the Reed-Sternberg and non-Hodgkin's lymphoma cells, whereas other somatic mutations were found exclusively in one or the other cell type.


CONCLUSIONS
In two patients with classic Hodgkin's disease and non-Hodgkin's B-cell lymphoma, we identified a common B-cell precursor, probably a germinal-center B-cell, for both lymphomas. This finding suggests that the two types of lymphoma underwent both shared and distinct transforming events and provides proof of the B-cell derivation of Reed-Sternberg cells in classic Hodgkin's disease.
Bräuninger
A
A
Department of Pathology, University of Frankfurt, Frankfurt am Main, Germany.
Hansmann
M L
ML
Strickler
J G
JG
Dummer
R
R
Burg
G
G
Rajewsky
K
K
Küppers
R
R
D000368:Aged; D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D005260:Female; D015321:Gene Rearrangement; D015322:Gene Rearrangement, B-Lymphocyte; D005803:Genes, Immunoglobulin; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D016539:Reed-Sternberg Cells / Q000276:immunology
D007135:Immunoglobulin Variable Region