Fig. 3.

EBV biology mirrors B cell biology. To the left is diagrammed a typical mucosal humoral immune response. Antigen in saliva crosses the epithelial barrier of the tonsil to be sampled by naïve B cells in the underlying lymphoid tissue. When naïve B cells recognize cognate antigen, they become activated blasts and migrate to the follicle to undergo a GC reaction. If they receive signals from antigen and antigen-specific Th cells, they can leave to become resting memory B cells that occasionally undergo division as part of memory B cell homeostasis. To the right is diagrammed how EBV uses the same pathways. EBV is spread through saliva, crosses the epithelial barrier, and infects naïve B cells. These become B cell blasts that enter the GC. Here, the viral latent proteins LMP1 and LMP2 have the capacity to provide surrogate antigen and Th survival signals that allow the latently infected B cells to leave the GC as resting memory cells that also divide through homeostasis. To the right are listed in orange the transcription programs used at each stage. The blue circles represent the viral DNA which is a circular episome