Epstein-Barr virus (EBV)-positive lymphoproliferations in post-transplant patients show immunoglobulin V gene mutation patterns suggesting interference of EBV with normal B cell differentiation processes
✍ Scribed by Andreas Bräuninger; Tilmann Spieker; Anja Mottok; Audrey Sylvia Baur; Ralf Küppers; Martin-Leo Hansmann
- Book ID
- 102162177
- Publisher
- John Wiley and Sons
- Year
- 2003
- Tongue
- English
- Weight
- 344 KB
- Volume
- 33
- Category
- Article
- ISSN
- 0014-2980
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✦ Synopsis
Abstract
In a model for persistent infection, Epstein‐Barr virus (EBV) uses the germinal center (GC) reaction to establish persistence in memory B cells. To study whether EBV adopts to normal B cell differentiation processes also in EBV‐associated lymphoproliferative diseases, we micromanipulated EBV^+^ cells from biopsies of five patients with post‐transplantation lymphoproliferative disease (PTLD) and one unusual Hodgkin lymphoma with many small EBV^+^ cells, and analyzed rearranged V genes of single cells. In all cases clonal expansions of EBV^+^ B cells were identified. The vast majority of these clones carried mutated V gene rearrangements and a fraction of clones showed ongoing hypermutation. Hence, PTLD likely derive from GC and/or post‐GC B cells. In two clones hypermutation occurred in the absence of follicular dendritic and CD4^+^ T cells, important interaction partners of normal GC B cells. Furthermore, in one case sustained somatic hypermutation occurred without expression of a functional antigen receptor. Hence, EBV^+^ B cells in PTLD can retain or acquire features of GC B cells in an unphysiological setting and may continue to undergo somatic hypermutation uncoupled from normal selection processes, suggesting that EBV interferes with normal B cell differentiation and selection processes in PTLD.