Frequent expansion of Epstein-Barr virus (EBV) infected cells in germinal centres of tonsils from an area with a high incidence of EBV-associated lymphoma.
Burkitt's lymphoma (BL) and Hodgkin's disease (HD) occurring in developing regions are frequently associated with Epstein-Barr virus (EBV) infection and have a high incidence in childhood. Recent genotyping studies indicate that the tumour cells of both neoplasms represent B cells that contain somatically mutated immunoglobulin heavy chain genes. This implies that the precursors of these neoplasms have participated in the germinal centre (GC) reaction. We therefore presumed that normal lymphoid tissues from children living in developing regions would harbour an increased number of EBV-infected cells within the GC, when compared with children living in industrialized nations. To test this hypothesis, hyperplastic tonsils from 40 children living in Bahia (Brazil) and 40 from German children were analysed for the presence of EBV-encoded small nuclear RNA (EBER) and EBV-encoded proteins by in situ hybridization and immunohistology, respectively. Although the overall EBV infection rate was similar in both groups (50 per cent of Bahian vs. 45 per cent of German cases), a significantly higher number of EBER-positive lymphoid cells were found in the GCs of 8/20 EBV-positive tonsils from Brazil (9-89 cells/GC; mean: 14.5 cells/GC per case), while only 3/18 tonsils from Germany displayed a few EBER positive cells (1-9 cells/GC; mean: 0.5 cell/GC per case) in this compartment (p < 0.007). In addition, the EBV-infected GC cells in Bahian samples resembled centroblasts, exhibited mitotic activity, and in two cases showed expression of EBV-encoded latent membrane protein (LMP)-1, findings not present in German samples. These data show that latently EBV-infected cells participate more frequently in GC reactions in developing regions than in industrialized countries and may abnormally express the oncogenic protein LMP-1. This could in part explain the higher incidence in this region of EBV association with lymphomas related to GC cells or their progeny, such as BL and HD.
Konsultations- und Referenzzentrum für Lymphknoten und Hämatopathologie at the Institute of Pathology, Klinikum Benjamin Franklin, Free University of Berlin, Germany.
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I
Araujo
H D
HD
Foss
M
M
Hummel
I
I
Anagnostopoulos
H S
HS
Barbosa
A
A
Bittencourt
H
H
Stein
D000293:Adolescent; D001938:Brazil; D002455:Cell Division; D002648:Child; D002675:Child, Preschool; D003906:Developing Countries; D020031:Epstein-Barr Virus Infections / Q000473:pathology*; D018858:Germinal Center / Q000473:pathology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D008223:Lymphoma / Q000821:virology*; D014066:Palatine Tonsil / Q000473:pathology / Q000821:virology*; D012367:RNA, Viral / Q000032:analysis; D017735:Virus Latency
C099537:Epstein-Barr virus encoded RNA 1; C106732:Epstein-Barr virus encoded RNA 2; D012367:RNA, Viral