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 a nd have a high incidence in childhood, Recent genotyping studies indicate t hat the tumour cells of both neoplasms represent B cells that contain somat ically mutated immunoglobulin heavy chain genes, This implies that the prec ursors of these neoplasms have participated in the germinal centre (GC) rea ction. We therefore presumed that normal lymphoid tissues from children liv ing 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 liv ing in Bahia (Brazil) and 40 from German children were analysed for the pre sence of EBV-encoded small nuclear RNA (EBER) and EBV-encoded proteins by i n situ hybridization and immunohistology, respectively. Although the overal l 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-positiv e lymphoid cells were found in the GCs of 8/20 EBV-positive tonsils from Br azil (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-infec ted GC cells in Bahian samples resembled centroblasts, exhibited mitotic ac tivity, and in two cases showed expression of EBV-encoded latent membrane p rotein (LMP)-1, findings not present in German samples. These data show tha t latently EBV-infected cells participate more frequently in CC reactions i n developing regions than in industrialized countries and may abnormally ex press the oncogenic protein LMP-1. This could in part explain the higher in cidence in this region of EBV association with lymphomas related to GC cell s or their progeny, such as BL and HD. Copyright (C) 1999 John Wiley & Sons , Ltd.