Secretion of anti-citrulline-containing peptide antibody by B lymphocytes in rheumatoid arthritis

Arthritis Rheum. 2001 Jan;44(1):41-7. doi: 10.1002/1529-0131(200101)44:1<41::AID-ANR6>3.0.CO;2-0.


Objective: To understand the regulation of anti-citrulline-containing peptide antibody (anti-CCP) production in rheumatoid arthritis (RA), production of anti-CCP by B cells derived from peripheral blood (PB), bone marrow (BM), and synovial fluid (SF) was examined.

Methods: Purified PB and SF B cells were isolated by negative selection and then cultured in the absence or presence of L-CD40 ligand cells and interleukin-10 or anti-CD3-activated T cells. Total IgM and IgM-anti-CCP were detected after 14 days of culture by enzyme-linked immunosorbent assay. Enzyme-linked immunospot assays were performed to analyze the frequency of cells that spontaneously produced IgM-anti-CCP in BM and SF B cells.

Results: IgM-anti-CCP autoantibodies were induced in PB B cells from healthy controls and RA patients following coculture with activated T cells or application of the CD40 activation system, whereas no production could be detected when PB B cells were cultured in the absence of a stimulus. SF and BM B cells from anti-CCP-seropositive RA patients, but not anti-CCP-seronegative patients, actively produced IgM-anti-CCP without stimulation. The frequency of spontaneous production of IgM-anti-CCP among the IgM-secreting cells ranged from 2.2% to 25%.

Conclusion: These results indicate the presence of B cell precursors for anti-CCP autoantibodies that are able to produce antibodies upon stimulation in the PB B cell repertoire of healthy controls and patients with RA. In contrast, B cells that actively secreted anti-CCP were specifically present in the BM and SF compartment of anti-CCP-seropositive RA patients. The local presence of anti-CCP-secreting cells in the inflamed joints provides evidence for an antigen-driven maturation of CCP-specific B cells at the site of inflammation in RA.

MeSH terms

  • Antibody Formation
  • Arthritis, Rheumatoid / blood*
  • Autoantibodies / metabolism
  • B-Lymphocytes / metabolism*
  • Citrulline / immunology*
  • Humans
  • Immunoglobulin M / blood
  • Synovial Fluid / cytology


  • Autoantibodies
  • Immunoglobulin M
  • Citrulline