title: Circulating plasmablasts/plasmacells as a source of anticitrullinated protein antibodies in patients with rheumatoid arthritis.
abstract: OBJECTIVE
  To study the characteristics and phenotype of anticitrullinated protein antibody (ACPA)-specific B cells in peripheral blood of patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Peripheral blood B cells from ACPA-positive patients with RA were cultured with or without stimulating factors. Following culture, supernatants were assessed for the presence of ACPA-IgG and non-specific total IgG by ELISA.
  
  
  RESULTS
  Following stimulation, ACPA were detectable in up to 100% of culture wells. Of interest, ACPA were also produced spontaneously by unstimulated peripheral blood mononuclear cells. In both cases, the average ACPA titre per culture well correlated with ACPA serum titres. No ACPA production was detectable in B cell cultures from ACPA-negative patients with RA or healthy controls. Importantly, FACS-sorting experiments located spontaneous ACPA production to the CD20 negative B cell population corresponding to circulating plasmablasts/cells.
  
  
  CONCLUSIONS
  ACPA-specific peripheral blood B cells are not confined to the CD20 positive memory pool, as circulating plasmablasts/cells spontaneously producing ACPA are also readily detectable. The latter points to an ongoing B cell immune response against citrullinated proteins and contrasts conventional immune responses against, for example, vaccines, where antigen-specific plasmablasts appear in peripheral blood only shortly after vaccination. These circulating, ACPA-specific plasmablasts/cells might represent targets for novel therapeutic interventions.
authors.affiliation: Department of Rheumatology, Leiden University Medical Centre, Leiden, The Netherlands.
authors.forename: Priscilla F
authors.initials: PF
authors.lastname: Kerkman
authors.forename: Yoann
authors.initials: Y
authors.lastname: Rombouts
authors.forename: Ellen I H
authors.initials: EI
authors.lastname: van der Voort
authors.forename: Leendert A
authors.initials: LA
authors.lastname: Trouw
authors.forename: Tom W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: René E M
authors.initials: RE
authors.lastname: Toes
authors.forename: Hans U
authors.initials: HU
authors.lastname: Scherer
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D010456:Peptides, Cyclic / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide
keywords: Ant-CCP; B cells; Rheumatoid Arthritis