EBV-associated Hodgkin lymphoma (HL) and some post-transplant lymphoproliferative disease (PTLD) cases originate from pro-apoptotic germinal center (GC) B cells that have acquired destructive somatic Ig V gene mutations and were presumably rescued from apoptosis by EBV. To find out whether B cell receptor-crippled GC B cells acquire features of HL and/or PTLD cells upon EBV-infection and to reveal the impact of EBV on expression of B cell differentiation markers, we compared lymphoblastoid cell lines (LCLs) from GC B cells (including BCR-crippled GC-LCLs) to monoclonal LCLs from naïve B cells (N-LCLs). In addition, we analyzed the controversially discussed effect of EBV-infection on the GC B-cell-specific process of somatic hypermutation in vitro. Irrespective of their cellular origin, LCLs expressed CD20, CD30, CD38, AID, Pu.1, and with one exception Syk, but lacked expression of the GC B cell marker BCL-6. Interestingly, the T cell transcription factor GATA-3 that is aberrantly expressed in HL was induced in most GC-LCLs and the memory B cell marker CD27 was activated in N-LCLs. Remarkably, only 4 of 24 GC-LCLs showed significant somatic hypermutation activity, demonstrating that EBV usually silences hypermutation upon infection of GC B cells. Notably, one of three N-LCL showed a low level of intraclonal diversification. Thus, EBV-infection deregulates multiple differentiation factors and processes in B cells, leading to a largely homogenous phenotype of EBV-infected B cells in latency III.