Molecular single-cell analysis of Hodgkin- and Reed-Sternberg cells harboring unmutated immunoglobulin variable region genes.
Hodgkin- and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease of the B lineage are the clonal progeny of antigen-experienced B cells harboring highly mutated immunoglobulin variable (V) region genes. Based on the detection of obviously destructive somatic mutations in a fraction of cases, we speculated that H/RS cells may be derived from a pre-apoptotic germinal center B cell. Seemingly contradicting this speculation, we present here the first case of classical Hodgkin's disease with H/RS cells harboring unmutated, potentially functional V region genes, which may indicate the derivation of the H/RS clone from a naive B cell. However, germinal center founder cells, which have not yet acquired somatic mutations, already have the intrinsic propensity to die by apoptosis. Thus, the rare occurrence of H/RS cells with unmutated V genes is expected if the H/RS cells are derived from the pool of pre-apoptotic germinal center B cells.
Müschen
M
M
Institute for Genetics, Department of Immunology, Universität zu Köln, Germany. markus.mueschen@uni-koeln.de
Küppers
R
R
Spieker
T
T
Bräuninger
A
A
Rajewsky
K
K
Hansmann
M L
ML
D000368:Aged; D020031:Epstein-Barr Virus Infections / Q000276:immunology / Q000473:pathology; D005260:Female; D018858:Germinal Center / Q000276:immunology / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000235:genetics; D006689:Hodgkin Disease / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000473:pathology; D008967:Molecular Biology; D009154:Mutation / Q000276:immunology; D016539:Reed-Sternberg Cells / Q000276:immunology* / Q000473:pathology*
D007135:Immunoglobulin Variable Region