Reed-Sternberg cells of classical Hodgkin's disease react with the plasma cell-specific monoclonal antibody B-B4 and express human syndecan-1.
Although the cellular origin of Reed-Sternberg (RS) cells of classical Hodgkin's disease (HD) has been a controversial issue for many years, recent immunophenotypic and molecular studies have suggested that RS cells of a subset of classical HD cases may be related to B cells. To further define the immunophenotypic features and the differentiation stage of RS cells, a series of 56 HD samples, including both nodular lymphocyte predominance (LP) (eight cases) and classical HD (nodular sclerosis [NS], 32 cases; mixed cellularity [MC], 16 cases) with a non-T-cell phenotype, were evaluated for the immunohistochemical expression of the B-B4 antigen, a specific marker for terminally differentiated B cells. Because the cDNA of the B-B4 antigen encodes syndecan-1, a member of a family of transmembrane heparan sulfate proteoglycans thought to be involved in binding cells of the B lineage to the interstitial matrix, the B-B4 immunoreactivity was correlated with the expression of syndecan-1 in HD-derived cell lines (L428, KM-H2), as detected by both reverse transcriptase polymerase chain reaction (RT-PCR) studies and Western blotting. Our results show that B-B4 reacts with RS cells and their morphological variants of all cases of classical HD, irrespective of their antigenic phenotype (B, undetermined), albeit at a varying degree of cellular expression. Notably, a high reactivity and staining intensity for the B-B4 monoclonal antibody (MoAb) was restricted to tumor cells from NS HD. In cases of the latter subtype, B-B4 positivity was also found in sclerosis-trapped spindle cells (fibrocytes/fibroblasts). Conversely, the putative tumor cells of nodular LP HD were consistently unreactive with the B-B4 MoAb. Finally, we have demonstrated by RT-PCR, flow cytometry, and Western blotting that cultured RS cells, of B and undetermined phenotype, express syndecan-1 mRNA and produce a form of syndecan-1, recognized by the B-B4 MoAb, which is predominantly associated with glycosaminoglycans and is present at the cell surface. Our detection of the plasma cell-specific antigen B-B4 (syndecan-1) on tumor cells of classical HD further supports that RS cell progenitors may be related to germinal/postgerminal center mature B cells and suggests that expression of syndecan-1 may contribute to some of the typical biologic and histopathologic features of classical HD, with a special regard to the NS subtype.
Carbone
A
A
Division of Pathology, Centro di Riferimento Oncologico, Istituto Nazionale di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
Gloghini
A
A
Gattei
V
V
Degan
M
M
Improta
S
S
Aldinucci
D
D
Canzonieri
V
V
Perin
T
T
Volpe
R
R
Gaidano
G
G
Zagonel
V
V
Pinto
A
A
D000911:Antibodies, Monoclonal / Q000276:immunology*; D000918:Antibody Specificity; D000943:Antigens, Differentiation / Q000032:analysis; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000276:immunology*; D015415:Biomarkers; D019070:Cell Lineage; D019337:Hematologic Neoplasms / Q000276:immunology / Q000473:pathology; D006689:Hodgkin Disease / Q000276:immunology / Q000473:pathology*; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology*; D011509:Proteoglycans / Q000096:biosynthesis / Q000276:immunology*; D016539:Reed-Sternberg Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053668:Syndecan-1; D053667:Syndecans
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D000951:Antigens, Neoplasm; D015415:Biomarkers; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans