Intrathecal production of immunoglobulins with an oligoclonal electrophoretic distribution pattern is a hallmark of the disease. These Bcell clones exhibit complex molecular characteristics and intraclonal diversity.Activation of B CellsWhat drives Bcell activation and clonal expansion is not fully understood. Epstein virus (EBV), a Blymphotropic microorganism, has been implicated in the development of the disease by epidemiological, immuneserological, and histological studies.64, 65 MS patients have intracerebral accumulation of EBVinfected B cells and plasma blasts, mostly in ectopic Bcell follicles,39 and a crossreactivity of the antiEBVspecific cells with CNS antigens has been noted.64, 65 Other mechanisms leading to autoimmune Bcell activation may be initiated by CD4 T helper type 2 (TH2) lymphocytes and their soluble inflammatory products (eg interleukine 4, 5, and 13),66 followed by an antigenspecific expansion of clones either in the peripheral circulation or in the damaged