Human immunodeficiency virus-associated Hodgkin's disease derives from post-germinal center B cells.
Human immunodeficiency virus-associated Hodgkin's disease (HIV-HD) displays several peculiarities when compared with HD of the general population. These include overrepresentation of clinically aggressive histologic types and frequent infection of Reed-Sternberg (RS) cells by Epstein-Barr virus (EBV). Recently, we have reported that the histogenesis of HD of the general population may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and of CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HIV-HD histogenesis and correlated their expression status to the virologic features of this disease. We have found that RS cells of all histologic categories of HIV-HD consistently display the BCL-6(-)/syn-1(+) phenotype and thus reflect post-GC B cells. Although BCL-6(-)/syn-1(+) RS cells of HIV-HD express CD40, they are not surrounded by CD40 ligand-positive (CD40L+) reactive T lymphocytes, which, in HD of the general population, are thought to regulate the disease phenotype through CD40/CD40L interactions. Conversely, RS cells of virtually all HIV-HD express the EBV-encoded latent membrane protein 1 (LMP1), which, being functionally homologous to CD40, may contribute, at least in part, to the modulation of the HIV-HD phenotype.
Carbone
A
A
Division of Pathology and the AIDS Program, Centro di Riferimento Oncologico, Istituto Nazionale Tumori, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Aviano, Italy. acarbone@ets.it
Gloghini
A
A
Larocca
L M
LM
Antinori
A
A
Falini
B
B
Tirelli
U
U
Dalla-Favera
R
R
Gaidano
G
G
D001402:B-Lymphocytes / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000032:analysis; D019013:CD40 Antigens / Q000032:analysis; D023201:CD40 Ligand; D002450:Cell Communication; D002454:Cell Differentiation; D004268:DNA-Binding Proteins / Q000032:analysis; D054278:Embryonal Carcinoma Stem Cells; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000473:pathology*; D018858:Germinal Center / Q000473:pathology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000209:etiology / Q000473:pathology* / Q000821:virology; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000473:pathology* / Q000821:virology; D008562:Membrane Glycoproteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000032:analysis; D014411:Neoplastic Stem Cells / Q000473:pathology* / Q000821:virology; D011509:Proteoglycans / Q000032:analysis; D011518:Proto-Oncogene Proteins / Q000032:analysis; D051560:Proto-Oncogene Proteins c-bcl-6; D016539:Reed-Sternberg Cells / Q000473:pathology* / Q000821:virology; D053668:Syndecan-1; D053667:Syndecans; D013601:T-Lymphocytes / Q000737:chemistry / Q000276:immunology; D014157:Transcription Factors / Q000032:analysis; D014763:Viral Matrix Proteins / Q000032:analysis
D014408:Biomarkers, Tumor; D019013:CD40 Antigens; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D011509:Proteoglycans; D011518:Proto-Oncogene Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; D014763:Viral Matrix Proteins; D023201:CD40 Ligand