Home LiteratureArticle Details
PMID: 8879220 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Hodgkin and Reed-Sternberg cells in Hodgkin's disease represent the outgrowth of a dominant tumor clone derived from (crippled) germinal center B cells.

The Journal of experimental medicine ·Vol. 184 ·No. 4 ·1996-10-01 ·Pages 1495-505

Kanzler H, Küppers R, Hansmann ML, Rajewsky K

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.

MeSH Terms
Adolescent Adult Amino Acid Sequence B-Lymphocytes Base Sequence Cell Lineage Female Gene Rearrangement, B-Lymphocyte Germinal Center Hodgkin Disease/genetics Humans Immunoglobulin Heavy Chains/genetics Immunoglobulin Variable Region/genetics Immunohistochemistry Male Micromanipulation Middle Aged Molecular Sequence Data Polymerase Chain Reaction Reed-Sternberg Cells Sequence Analysis, DNA
Chemicals
Immunoglobulin Heavy Chains Immunoglobulin Variable Region
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kanzler H
Institute for Genetics, University of Cologne, Germany.
Küppers R
Hansmann M L
Rajewsky K
References (42)
42 references, click to expand
  1. Report of the Committee on Hodgkin's Disease Staging Classification.
    Cancer Res. 1971 Nov;31(11):1860-1 PMID: 5121694
  2. Numerical chromosome aberrations are present within the CD30+ Hodgkin and Reed-Sternberg cells in 100% of analyzed cases of Hodgkin's disease.
    Blood. 1995 Aug 15;86(4):1464-8 PMID: 7632954
  3. Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.
    EMBO J. 1988 Mar;7(3):727-38 PMID: 3396540
  4. Isolation of Reed-Sternberg cells from lymph nodes of Hodgkin's disease patients.
    Blood. 1989 Jan;73(1):222-9 PMID: 2910360
  5. Hodgkin's disease with monoclonal and polyclonal populations of Reed-Sternberg cells.
    N Engl J Med. 1995 Oct 5;333(14):901-6 PMID: 7545266
  6. Hodgkin cells accumulate mRNA for bcl-2.
    Lab Invest. 1995 Oct;73(4):492-6 PMID: 7474920
  7. Somatic hypermutation.
    Curr Opin Immunol. 1995 Apr;7(2):248-54 PMID: 7546385
  8. Immunoglobulin V genes in Reed-Sternberg cells.
    N Engl J Med. 1996 Feb 8;334(6):404; author reply 405-6 PMID: 8538724
  9. Immunoglobulin V genes in Reed-Sternberg cells.
    N Engl J Med. 1996 Feb 8;334(6):404-5; author reply 405-6 PMID: 8538725
  10. Immunoglobulin V genes in Reed-Sternberg cells.
    N Engl J Med. 1996 Feb 8;334(6):405-6 PMID: 8538726
  11. Molecular single cell analysis demonstrates the derivation of a peripheral blood-derived cell line (L1236) from the Hodgkin/Reed-Sternberg cells of a Hodgkin's lymphoma patient.
    Blood. 1996 Apr 15;87(8):3429-36 PMID: 8605361
  12. Epstein-Barr Virus DNA recombination and loss in sporadic Burkitt's lymphoma.
    J Infect Dis. 1996 Mar;173(3):529-35 PMID: 8627013
  13. Genetic instability in patients with Hodgkin's disease undergoing chemotherapy.
    J Clin Invest. 1995 Dec;96(6):2744-7 PMID: 8675643
  14. Molecular Ig gene analysis reveals that monocytoid B cell lymphoma is a malignancy of mature B cells carrying somatically mutated V region genes and suggests that rearrangement of the kappa-deleting element (resulting in deletion of the Ig kappa enhancers) abolishes somatic hypermutation in the human.
    Eur J Immunol. 1996 Aug;26(8):1794-800 PMID: 8765023
  15. Expression of CD95 antigen and Bcl-2 protein in non-Hodgkin's lymphomas and Hodgkin's disease.
    Am J Pathol. 1996 Mar;148(3):847-53 PMID: 8774139
  16. Molecular single-cell analysis of Hodgkin and Reed-Sternberg cells.
    Mol Med Today. 1995 Apr;1(1):26-30 PMID: 9415134
  17. Detection of Epstein-Barr viral genomes in Reed-Sternberg cells of Hodgkin's disease.
    N Engl J Med. 1989 Feb 23;320(8):502-6 PMID: 2536894
  18. Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1-positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization.
    Blood. 1989 Aug 1;74(2):810-6 PMID: 2546633
  19. High gradient magnetic cell separation with MACS.
    Cytometry. 1990;11(2):231-8 PMID: 1690625
  20. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death.
    Cell. 1991 Jun 28;65(7):1107-15 PMID: 1648447
  21. In vivo somatic mutation in the lymphocytes of Hodgkin's disease patients.
    Environ Mol Mutagen. 1991;18(1):6-13 PMID: 1713845
  22. Germinal center cells express bcl-2 protein after activation by signals which prevent their entry into apoptosis.
    Eur J Immunol. 1991 Aug;21(8):1905-10 PMID: 1868875
  23. Molecular characterization of the human immunoglobulin V lambda I germline gene repertoire.
    Mol Immunol. 1992 Sep;29(9):1031-42 PMID: 1495496
  24. Clonal evolution of a follicular lymphoma: evidence for antigen selection.
    Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6770-4 PMID: 1495966
  25. Recent results on the biology of Hodgkin and Reed-Sternberg cells. I. Biopsy material.
    Leuk Lymphoma. 1992 Nov;8(4-5):283-313 PMID: 1337848
  26. Structure and physical map of 64 variable segments in the 3'0.8-megabase region of the human immunoglobulin heavy-chain locus.
    Nat Genet. 1993 Jan;3(1):88-94 PMID: 8490662
  27. Single-cell analysis of Hodgkin and Reed-Sternberg cells: molecular heterogeneity of gene expression and p53 mutations.
    Blood. 1993 Jun 1;81(11):3097-115 PMID: 8499644
  28. Human IgM+IgD+ B cells, the major B cell subset in the peripheral blood, express V kappa genes with no or little somatic mutation throughout life.
    Eur J Immunol. 1993 Dec;23(12):3272-7 PMID: 8258343
  29. Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections.
    EMBO J. 1993 Dec 15;12(13):4955-67 PMID: 8262038
  30. The variable genes of the human immunoglobulin kappa locus.
    Biol Chem Hoppe Seyler. 1993 Nov;374(11):1001-22 PMID: 8292259
  31. Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity.
    Am J Surg Pathol. 1994 May;18(5):526-30 PMID: 8172327
  32. Detection of immunoglobulin heavy-chain gene rearrangement at the single-cell level in malignant lymphomas: no rearrangement is found in Hodgkin and Reed-Sternberg cells.
    Int J Cancer. 1994 Jun 15;57(6):799-804 PMID: 8206675
  33. Analysis of somatic mutation in five B cell subsets of human tonsil.
    J Exp Med. 1994 Jul 1;180(1):329-39 PMID: 8006591
  34. The cellular biology of the Reed-Sternberg cell.
    Blood. 1994 Aug 15;84(4):1005-19 PMID: 8049419
  35. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group.
    Blood. 1994 Sep 1;84(5):1361-92 PMID: 8068936
  36. A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q.
    Nat Genet. 1994 Jun;7(2):162-8 PMID: 7920635
  37. Variable region gene analysis of B cell subsets derived from a 4-year-old child: somatically mutated memory B cells accumulate in the peripheral blood already at young age.
    J Exp Med. 1994 Oct 1;180(4):1383-93 PMID: 7931072
  38. The Reed-Sternberg cells of Hodgkin disease are clonal.
    Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):9842-6 PMID: 7937902
  39. Hodgkin disease: Hodgkin and Reed-Sternberg cells picked from histological sections show clonal immunoglobulin gene rearrangements and appear to be derived from B cells at various stages of development.
    Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10962-6 PMID: 7971992
  40. New characterization of infectious mononucleosis and a phenotypic comparison with Hodgkin's disease.
    Am J Pathol. 1995 Feb;146(2):379-88 PMID: 7531953
  41. A novel form of Epstein-Barr virus latency in normal B cells in vivo.
    Cell. 1995 Feb 24;80(4):593-601 PMID: 7532548
  42. Rearranged antigen receptor genes in Hodgkin's disease.
    Blood. 1987 Jul;70(1):96-103 PMID: 2954598
Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.184.4.1495
Published
1996-10-01
Pages
1495-505
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2192840
Subset
IM
Databases
GENBANK
Z77316, Z77317, Z77318, Z77319, Z77320, Z77321, Z77322, Z77323, Z77324, Z77325, Z77326, Z77327, Z77328, Z77329, Z77330, Z77331
External Links
PubMed source DOI: 10.1084/jem.184.4.1495 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2