Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1998 Nov;153(5):1609-14.
doi: 10.1016/S0002-9440(10)65749-5.

Immunoglobulin VH gene mutational analysis suggests that primary effusion lymphomas derive from different stages of B cell maturation

A Matolcsy  1 , R G Nádor, E Cesarman, D M Knowles
Affiliations

Immunoglobulin VH gene mutational analysis suggests that primary effusion lymphomas derive from different stages of B cell maturation

A Matolcsy et al. Am J Pathol. 1998 Nov.

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.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Deduced amino acid sequences of Ig VH-(D)-JH regions of the tumor-derived clones (A–H) from seven patients with PEL. Comparisons are made with the closest germline VH genes. The proportion of the CDR3 corresponding to the D and JH segments are not shown. The individual FR and CDR regions are indicated according to Kabat et al (1991). Identity with the VH germline sequences is shown by dots, replacement mutations by uppercase letters, and silent mutations by lowercase letters.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Knowles DM, Inghirami G, Ubriaco A, Dalla-Favera R: Molecular genetic analysis of three AIDS-associated neoplasms of uncertain lineage demonstrates their B-cell derivation and the possible pathogenetic role of the Epstein-Barr virus. Blood 1989, 73:792-799 - PubMed
    1. Walts AE, Shintaku IP, Said JW: Diagnosis of malignant lymphoma in effusions from patients with AIDS by gene rearrangement. Am J Clin Pathol 1990, 94:170-175 - PubMed
    1. Karcher DS, Dawkins F, Garrett CT, Schulof RS: Body cavity-based non-Hodgkin’s lymphoma (NHL) in HIV-infected patients, and genotypic features. Lab Invest 1992, 66:80 (abstr)
    1. Green I, Espiritu E, Ladanyi M, Chaponda R, Wieczorek R, Gallo L, Feiner H: Primary lymphomatous effusions in AIDS: a morphological, immunophenotypic, and molecular study. Modern Pathol 1995, 8:39-45 - PubMed
    1. Cesarman E, Chang Y, Moore PS, Said JW, Knowles DM: Kaposi’s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas. N Engl J Med 1995, 332:1186-1191 - PubMed

Publication types

Substances

LinkOut - more resources