Patterns of Epstein-Barr virus infection in non-neoplastic lymphoid tissue

Abstract

Taking advantage of the abundant expression of the small Epstein-Barr virus (EBV)-encoded RNAs (EBERs) in latently infected cells, we have analyzed 72 normal and hyperplastic lymph nodes and three tonsils of acute infectious mononucleosis (IM) for the presence and distribution of EBV+ cells using EBER-specific in situ hybridization, in some cases combined with immunohistologic demonstration of cell type- characteristic antigens. In IM, large numbers of EBV+ lymphoid B blasts were detectable in extrafollicular areas, whereas germinal centers were generally free of EBV+ cells. In reactive lymph nodes, the frequency of EBV+ cells varied with the degree of lymphoid hyperplasia and underlying immune status. The lowest numbers of EBV+ cells were detected in nonactivated lymph nodes and highest in human immunodeficiency virus-associated lymphadenopathy. If present in these lymph nodes, EBV+ cells were almost exclusively localized to extrafollicular areas, as also observed in IM. However, in contrast to IM, these cells were mainly small lymphocytes. Furthermore, in some instances, occasional scattered EBV+ cells were seen within germinal centers, and in two cases diffuse expansions of EBV+ cells occurred within a single germinal center each, indicating that under certain circumstances EBV+ B lymphocytes may participate in physiologic germinal center reactions. These findings reflect the interference of EBV with physiologic lymphoid differentiation pathways and provide a link to EBV-associated malignant lymphomas with a postulated origin from germinal center cells.

The Epstein–Barr virus and the pathogenesis of lymphoma

“…It may be that this is such an infrequent event as to be mostly undetectable in tissue sections [38]. We and others have reported instances of reactive lymphadenopathy with expansions of EBV-positive cells within one or more GC [43][44][45][46][47][48] (Figure 2). This phenomenon is more commonly observed in patients with an underlying immunodeficiency, such as HIV infection, or in adult late-onset EBV-associated B-cell lymphoproliferations associated with an age-related decline in EBV-specific immunity [48].…”

Detection of EBV RNA (EBER‐1 and EBER‐2) in Malaria Lymph Nodes by In Situ Hybridization

“…However, during periods of prolonged B cell activation, as occurs in malaria, their number in the circulation increases along with the general number of lymphocytes, and EBER+ cells become more frequently detectable within the lymph nodes. Around 33% of `reactive' lymph nodes are EBER+ with the frequency of positive cells varying with the degree of lymphoid hyperplasia and underlying immune status (15). During periods of acute P falciparum malaria, which is accompanied by an impaired EBV-specific cytotoxic T cell control (5) and increased frequency of EBV transformation of B cells (7), African children have elevated numbers of circulating EBV+ B cells-five times that seen following antimalarial chemotherapy (11).…”

Low prevalence of latently Epstein‐Barr virus‐infected cells in chronic gastritis

“…Paraffin sections from all biopsies were subjected to in situ hybridization with probes specific for the small EBV-encoded RNAs (EBER1 and EBER2) as described previously (Niedobitek et al, 1992;Spieker and Herbst, 2000). Single-stranded RNA probes were generated by in vitro transcription using the plasmids pBSJJJ1 and pBSJJJ2.…”

“…In Erlangen, cases were hybridized with [ 35 S]-labeled probes. Labeling of probes, hybridization, and washing conditions as well as the methods for the detection of probes have been described previously (Niedobitek et al, 1992;Spieker and Herbst, 2000). As in previous studies, antisense probes specific for EBER1 and EBER2 were mixed to increase sensitivity.…”