Cell origin of pyothorax-associated lymphoma: a lymphoma strongly associated with Epstein-Barr virus infection

• Published in: Leukemia Vol. 22; no. 3; pp. 620 - 627
• Main Authors: TAKAKUWA, T, TRESNASARI, K, RAHADIANI, N, MIWA, H, DAIBATA, M, AOZASA, K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.03.2008; Nature Publishing Group
• Subjects: Aged; Amino Acid Sequence; Azacytidine; B-cell lymphoma; B-Lymphocyte Subsets - pathology; B-Lymphocyte Subsets - virology; Biological and medical sciences; Cell Line, Tumor; Cell Lineage; Cell Transformation, Viral; Chains; Complications and side effects; Demethylation; Deoxyribonucleic acid; Diagnosis; DNA; Empyema, Pleural - complications; Epstein-Barr virus; Epstein-Barr virus diseases; Epstein-Barr Virus Infections - pathology; Female; Gene expression; Gene Rearrangement, B-Lymphocyte; Genes, Immunoglobulin; Genetic aspects; Genetic transformation; Genotypes; Heavy chains; Hematologic and hematopoietic diseases; Herpesvirus 4, Human - pathogenicity; Humans; Immunoglobulins; Infections; Infectious diseases; Light chains; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Large B-Cell, Diffuse - virology; Lymphopoiesis; Male; Medical sciences; Middle Aged; Molecular Sequence Data; mRNA; Mutation; Neoplasm Proteins - genetics; Non-Hodgkin's lymphomas; Pleural cavity; Pleural Neoplasms - pathology; Pleural Neoplasms - virology; Polymerase chain reaction; Risk factors; Sequence Alignment; Sequence Homology, Amino Acid; Somatic Hypermutation, Immunoglobulin; Transcriptional Activation; Viral diseases; Viruses; Japan; Gammaherpesvirinae; Heavy peptide chain; Immunoglobulins; Hematology; Herpesviridae; Selection; B-Lymphocyte; Epstein Barr virus; Lymphoid neoplasm; IgH; Virus; Antigen; Infection; Associated virus; postgerminal center B cell; Viral disease; EBV; Pyothorax associated lymphoma; pyothorax-associated lymphoma; antigen- selection; Cell origin
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2405059

Pyothorax-associated lymphoma (PAL) is an Epstein-Barr virus (EBV)-associated B cell lymphoma developing in the pleural cavity affected by chronic pyothorax. To clarify the cell origin of PAL, the expression of immunoglobulin heavy (IgH) and light chains in relation to somatic hypermutations (SHMs) of rearranged Ig heavy- and light-chain variable (IgV(H), IgV(L)) genes was examined using cell lines as well as clinical samples. SHMs without ongoing mutations of the IgV(H) gene were found in all PAL cell lines and clinical samples available for sequencing, indicating PAL to be derived from B cells at the postgerminal center (GC) stage of the differentiation process. They could be subdivided into post-GC cells with potentially productive IgV(H) genotypes (Group 1) and with sterile IgV(H) genotypes (Group 2). IgH expression was abrogated in Group 2 as expected and also in two cell lines in Group 1. DNA demethylation experiments with 5-aza-dC induced expression of IgH mRNA and protein in these cell lines. Most PAL cells were derived from crippled post-GC cells, which usually could not survive. Transformation of such B cells through EBV infection might provide a basis for the development of PAL with additional genetic changes.