E pstein– B arr virus infection transforms CD 25 + B cells into antibody‐secreting cells in rheumatoid arthritis patients

Summary Epstein–Barr virus ( EBV ) infection may initiate production of autoantibodies and development of cancer and autoimmune diseases. Here we outline phenotypic and functional changes in B cells of patients with rheumatoid arthritis ( RA ) related to EBV infection. The B‐cell phenotype was analysed in blood and bone marrow ( BM ) of RA patients who had EBV transcripts in BM ( EBV + , n  = 13) and in EBV − ( n  = 22) patients with RA. The functional effect of EBV was studied in the sorted CD 25 + and CD 25 − peripheral B cells of RA patients ( n  = 18) and healthy controls ( n  = 9). Rituximab treatment results in enrichment of CD 25 + B cells in peripheral blood ( PB ) of EBV + RA patients. The CD 25 + B‐cell subset displayed a more mature phenotype accumulating IgG‐expressing cells. It was also enriched with CD 27 + and CD 95 + cells in PB and BM . EBV stimulation of the sorted CD 25 + B cells in vitro induced a polyclonal IgG and IgM secretion in RA patients, while CD 25 + B cells of healthy subjects did not respond to EBV stimulation. CD 25 + B cells were enriched in PB and synovial fluid of RA patients. EBV infection affects the B‐cell phenotype in RA patients by increasing the CD 25 + subset and by inducing their immunoglobulin production. These findings clearly link CD 25 + B cells to the EBV ‐dependent sequence of reactions in the pathogenesis of RA .