AID expression in EBV-infected cells in vivo. (A) Double-labeling EBER-specific in situ hybridization (black grains) and AID immunohistochemistry (red staining) of a tonsil from a patient with infectious mononucleosis (IM) shows that most EBV-infected cells are AID negative. Conversely, a significant number of AID-positive cells were also EBV⁺ (eg, arrow). (B) In a hyperplastic tonsil from a patient with persistent EBV infection, AID expression is detected in germinal center (GC) cells, while scattered extrafollicular EBV⁺ cells (arrows) are AID negative. (C) Double-labeling immunofluorescence of an IM tonsil shows that most EBNA2-positive cells (red) are AID negative (green) and vice versa, while only few EBNA2-positive cells coexpressing AID were identified (inset). (D) Double-labeling immunofluorescence also reveals that AID (green) and LMP1 (red) are expressed in nonoverlapping cell populations.