title: Epstein-Barr virus infection transforms CD25+ B cells into antibody-secreting cells in rheumatoid arthritis patients.
abstract: 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.
authors.affiliation: EULAR Centre of Excellence, Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Brisslert
authors.forename: Maria
authors.initials: M
authors.lastname: Rehnberg
authors.forename: Maria I
authors.initials: MI
authors.lastname: Bokarewa
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002472:Cell Transformation, Viral / Q000276:immunology*; D002478:Cells, Cultured; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology* / Q000821:virology; D005260:Female; D004854:Herpesvirus 4, Human / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D053645:Interleukin-2 Receptor alpha Subunit / Q000097:blood*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D001323:Autoantibodies; D015415:Biomarkers; C508017:IL2RA protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053645:Interleukin-2 Receptor alpha Subunit; D000069283:Rituximab
keywords: CD25+ B cells; Epstein-Barr virus; anti-CD20 treatment; bone marrow; rheumatoid arthritis