title: Distinct cellular origins of primary effusion lymphoma with and without EBV infection.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) is associated with three distinct lymphoproliferative disorders: primary effusion lymphoma (PEL), multicentric Castleman's disease (MCD) and germinotropic lymphoproliferative disorder (GLD). KSHV positive lymphocytes in GLD and in most cases of PEL are co-infected by Epstein-Barr virus (EBV) and these viral double positive cells harbour mutated rearranged immunoglobulin (Ig) genes, suggesting that they originate from germinal centre or post-germinal centre B-cells. In contrast, KSHV positive cells in MCD are invariably negative for EBV, do not carry Ig gene mutation and are believed to originate from naïve IgMlambda expressing B-cells. Interestingly, one EBV negative PEL (BC3) also lacks Ig gene mutation, raising the question whether KSHV preferentially targets naïve B-cells in the absence of EBV. We compared the cellular origin of PEL with and without EBV infection by analysis of Ig gene mutation. High molecular weight DNA from 17 PELs was subjected to PCR of the rearranged Ig heavy and light chain genes. Successful amplification was achieved from eight cases (four EBV positive and four EBV negative) and the PCR products were sequenced. All four EBV positive PEL showed variable levels of mutation in their rearranged V(H) or V(L) genes, ranging from 4 to 7%. In contrast, two of the four EBV negative PELs including BC3 displayed absence of mutation in their rearranged Ig genes. Our results indicate that EBV positive PELs are derived from germinal centre or post-germinal centre B-cells, whereas EBV negative PELs may originate from either germinal/post-germinal centre or naïve B-cells.
authors.affiliation: Department of Histopathology, Royal Free and University College Medical School, University College London, Rockefeller Building, University Street, London WC1E 6JJ, UK.
authors.forename: Rifat
authors.initials: R
authors.lastname: Hamoudi
authors.forename: Tim C
authors.initials: TC
authors.lastname: Diss
authors.forename: Eric
authors.initials: E
authors.lastname: Oksenhendler
authors.forename: Langxing
authors.initials: L
authors.lastname: Pan
authors.forename: Antonino
authors.initials: A
authors.lastname: Carbone
authors.forename: Valeria
authors.initials: V
authors.lastname: Ascoli
authors.forename: Chris
authors.initials: C
authors.lastname: Boshoff
authors.forename: Peter
authors.initials: P
authors.lastname: Isaacson
authors.forename: Ming-Qing
authors.initials: MQ
authors.lastname: Du
mesh_terms: D000818:Animals; D001483:Base Sequence; D020031:Epstein-Barr Virus Infections / Q000150:complications; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005803:Genes, Immunoglobulin; D004854:Herpesvirus 4, Human; D006801:Humans; D008223:Lymphoma / Q000235:genetics* / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction