A cardinal feature of multiple sclerosis (MS) is the persistent intrathecal 
synthesis of antibodies. Our previous finding that a large fraction of B cells 
infiltrating the MS brain are infected with Epstein-Barr virus (EBV) raises the 
possibility that this virus, because of its ability to establish a latent 
infection in B cells and interfere with their differentiation, contributes to 
B-cell dysregulation in MS. The aim of this study was to gain further insight 
into EBV latency programs and their relationship to B-cell activation in the MS 
brain. Immunohistochemical analysis of postmortem MS brain samples harboring 
large EBV deposits revealed that most B cells in white matter lesions, meninges, 
and ectopic B-cell follicles are CD27+ antigen-experienced cells and coexpress 
latent membrane protein 1 and latent membrane protein 2A, 2 EBV-encoded proteins 
that provide survival and maturation signals to B cells. By combining 
laser-capture microdissection with preamplification reverse 
transcription-polymerase chain reaction techniques, EBV latency transcripts 
(latent membrane protein 2A, EBV nuclear antigen 1) were detected in all MS 
brain samples analyzed. We also found that B cell-activating factor of the tumor 
necrosis factor family is expressed in EBV-infected B cells in acute MS lesions 
and ectopic B-cell follicles. These findings support a role for EBV infection in 
B-cell activation in the MS brain and suggest that B cell-activating factor of 
the tumor necrosis factor family produced by EBV-infected B cells may contribute 
to this process resulting in viral persistence and, possibly, disruption of 
B-cell tolerance.