title: Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells.
abstract: In Hodgkin's disease (HD), the Hodgkin and Reed-Sternberg (HRS) cells represent only a minute population in the diseased tissue. The investigation of lineage derivation and clonal origin of these cells has yielded conflicting results. We have analyzed HRS cells micromanipulated from infiltrated tissue sections of 10 primary HD patients for rearranged V genes, extending a previous study. Clonally related rearrangements were found in nine cases, indicating that HRS cells represent a dominant clone of B lineage-derived cells in at least a large fraction of cases of HD. Rearranged VH genes from HRS cells carried a high load of somatic mutation, indicating that HRS cells are derived from germinal center (GC) cells or their progeny. Stop codons in some in-frame V gene rearrangements suggest that the HRS cell precursors reside inside GCs, have acquired crippling mutations that prevent antigenic selection, but escape apoptosis through some transforming event.
authors.affiliation: Institute for Genetics, University of Cologne, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Kanzler
authors.forename: R
authors.initials: R
authors.lastname: Küppers
authors.forename: M L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: K
authors.initials: K
authors.lastname: Rajewsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D001402:B-Lymphocytes; D001483:Base Sequence; D019070:Cell Lineage; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D018858:Germinal Center; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D008846:Micromanipulation; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016539:Reed-Sternberg Cells; D017422:Sequence Analysis, DNA
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region