The impact of B cells in MS has been suggested by their presence in the cerebrospinal fluid of patients with the disease.⁷ In addition, B cells have a receptor for EBV and may become immortalized after in vitro infection with the virus.⁷ A recent investigation of the potential link between the 2 diseases sought to determine whether gene expression and transcription networks in EBV-transformed B cells varied between patients with MS and their healthy siblings.⁷ Differential expression of several genes was apparent. In the samples from the MS patients, the gene products TCF2, CXCL10, and FUT4 were up-regulated, whereas CDC5L, TNFRSF19, and HLA-DR were down-regulated. Two intersecting clusters of transcriptional factors were identified, a larger one governed by the up-regulated TCF2 and a smaller one regulated by the down-regulated CDC5L. Previous work had demonstrated that TCF2 up-regulates chemokine receptor 1 (CCR1; CC motif), a molecule expressed on T cells and macrophages.^7,8 Numerous CCR1-positive infiltrating macrophages were found in MS plaques. CCR1 has also been linked to newly infiltrated monocytes in MS lesions. These and other observations have led researchers to propose that TCF2 may play a central role in the pathogenesis of MS.⁷ No role has yet been characterized for CDC5L.

Additional evidence has suggested that EBV persistence and reactivation in the CNS may be a key contributor to the development of MS.⁹ Postmortem examination of brain tissue from MS patients revealed evidence of EBV infection in a substantial proportion of brain-infiltrating B cells as well as in plasma cells (in nearly 100% of cases). Abnormal accumulation of EBV-infected cells did not correlate with disease course or duration, gender, age at disease onset, or immunosuppressive therapy. Furthermore, no such findings were evident in cases involving other inflammatory neurologic diseases.⁹

Another line of inquiry has been prompted by epidemiologic evidence showing that individuals with low vitamin D levels are more prone to develop MS.^10,11 Notably, vitamin D receptors are expressed on B cells infected by EBV, on antigen-presenting cells, and on activated lymphocytes.¹² Moreover, dihydroxyvitamin D₃ (the isoactive metabolite of vitamin D) suppresses antibody production and T-cell proliferation; the T cells also trend toward a less detrimental Th2 phenotype. Vitamin D may therefore protect against MS by modulating the immune response to EBV. It has been suggested in this regard that Theiler’s murine encephalomyelitis virus model of MS may be appropriate for studying the impact of vitamin D supplementation.¹² This is because demyelinating disease may also be induced in mice by Theiler’s virus, which triggers T cells to become progressively more responsive to myelin epitopes. Thus, studies of vitamin D supplementation or deprivation in Theiler’s model could provide further insight into the interrelation of immune responses to viruses and vitamin D in MS.¹² However, such studies have yet to be conducted.

Evidence of links between B cells, EBV, and MS appears to be mounting. Future studies may shed more light on these associations, potentially leading to novel therapeutic interventions as well as strategies for preventing MS.