title: Immunoglobulin VH gene mutational analysis suggests that primary effusion lymphomas derive from different stages of B cell maturation.
abstract: Primary effusion lymphoma (PEL) is a recently described distinct subtype of non-Hodgkin's lymphoma associated with infection by the Kaposi's sarcoma-associated herpesvirus, also called human herpesvirus-8. Most cases of PEL are also associated with the Epstein-Barr virus (EBV). In order to better characterize the cellular origin of PEL, we investigated the immunoglobulin (Ig) heavy chain variable region (VH,) genes expressed by tumor cells of the BC-1 and BC-3 cell lines derived from PELs and five original PEL specimens. In the six EBV-positive PELs examined, including the BC-1 cell line, the expressed VH gene sequences showed numerous point mutations relative to the putative germline VH gene sequences. In addition, the VH, segment of one of these cases showed intraclonal sequence heterogeneity, indicating ongoing somatic mutation. In five cases, the distribution and type of mutations indicated that tumor cells had been selected by antigen. Because somatically mutated Ig genes are expressed by B cells that have reached a germinal center/post-germinal center stage of development, these findings suggest that the PEL cell of origin is a germinal center or post-germinal center B cell in most cases. In contrast, the VH gene segment expressed by tumor cells of the BC-3 cell line, which was originated from an EBV-negative PEL obtained from an HIV-negative patient, was unmutated, suggesting a pre-germinal center B cell origin for tumor cells of this particular PEL cell line. Taken together, these findings suggest that development of PELs may not be restricted to one stage of B cell differentiation and may represent transformation of B cells at different stages of ontogeny.
authors.affiliation: Department of Pathology, University Medical School of Pécs, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Matolcsy
authors.forename: R G
authors.initials: RG
authors.lastname: Nádor
authors.forename: E
authors.initials: E
authors.lastname: Cesarman
authors.forename: D M
authors.initials: DM
authors.lastname: Knowles
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D004252:DNA Mutational Analysis; D015723:Gene Library; D005803:Genes, Immunoglobulin / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D016130:Immunophenotyping; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000276:immunology; D008969:Molecular Sequence Data; D016066:Pleural Effusion, Malignant / Q000235:genetics* / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region