Epstein- Barr virus infection transforms CD25+ B cells into antibody-secreting cells in rheumatoid arthritis patients.

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 CD25⁺ and CD25⁻ peripheral B cells of RA patients ( n = 18) and healthy controls ( n = 9). Rituximab treatment results in enrichment of CD25⁺ B cells in peripheral blood ( PB) of EBV⁺ RA patients. The CD25⁺ B-cell subset displayed a more mature phenotype accumulating IgG-expressing cells. It was also enriched with CD27⁺ and CD95⁺ cells in PB and BM. EBV stimulation of the sorted CD25⁺ B cells in vitro induced a polyclonal IgG and IgM secretion in RA patients, while CD25⁺ B cells of healthy subjects did not respond to EBV stimulation. CD25⁺ 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 CD25⁺ subset and by inducing their immunoglobulin production. These findings clearly link CD25⁺ B cells to the EBV-dependent sequence of reactions in the pathogenesis of RA. [ABSTRACT FROM AUTHOR]