The human herpesviruses Epstein-Barr virus (EBV) and, supporting an essential role of EBV in HL lymphomagenesis (1). EBV ϩ HRS cells express the viral protein latent membrane protein 2A (LMP2A), which can functionally replace the BCR because Ig-negative B cells can only survive if infected with EBV but not with an LMP2A-negative EBV mutant (4). BCR and LMP2A both contain an immunoreceptor tyrosine-based activation motif (ITAM) (5, 6), which is central for the induction of BCR signaling cascades. In contrast to the BCR, LMP2A is thought to be constitutively active and independent of any ligand or antigen encounter (references 7 and 8 and references therein). EBV also encodes LMP1, a constitutive CD40 receptor mimic that provides a second survival signal for B cells. LMP1 together with LMP2A activates HRS cells, protects them from apoptosis, and induces their proliferation (1, 9).PEL tumor cells are infected with KSHV, and ca. 80% are EBV ϩ , although LMP1 and LMP2A are barely expressed (10,11