CD21−/low B cells associate with joint damage in rheumatoid arthritis patients

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Depletion of B cells is beneficial in rheumatoid arthritis (RA) patients with autoantibodies to citrullinated proteins (ACPA) and/or the Fc portion of immunoglobulins (rheumatoid factor [RF]), suggesting a role for B cells in disease pathogenesis. To date, however, the identity of specifically pathogenic B cell subsets has not been discovered. One candidate population is identified by the low expression or absence of complement receptor 2 (CD21−/low B cells). In this study, we sought to determine whether there was any correlation between CD21−/low B cells and clinical outcome in patients with established RA, either ACPA+/RF+ (n = 27) or ACPA/RF (n = 10). Healthy donors (n = 17) were included as controls. The proportion of the CD21−/low CD27IgD memory B cell subset in peripheral blood (PB) was significantly increased in ACPA+/RF+ RA patients compared with healthy donors, and the frequency of this subset correlated with joint destruction (r = 0.57, P < 0.04). The levels of the chemokines CXCL-9 and CXCL-10 were higher in synovial fluid than in plasma, and PB CD21−/low cells expressed the receptor, CXCR3. In synovial fluid, most of the B cells were CD21−/low, approximately 40% of that population was CD27IgD, and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor κB ligand (RANKL). This subset also secreted RANKL, in addition to other factors such as IL-6, even in the absence of stimulation. We interpret these data as reason to propose the hypothesis that the CD27IgD subset of CD21−/low B cells may mediate joint destruction in patients with ACPA+/RF+ RA.


  • Katrin Thorarinsdottir
  • Alessandro Camponeschi
  • Charlotte Jonsson
  • Karin Granhagen Önnheim
  • Jenny Nilsson
  • Kristina Forslind
  • Marcella Visentini
  • Lennart Jacobsson
  • Inga Lill Mårtensson
  • Inger Gjertsson
External organisations
  • University of Gothenburg
  • Helsingborg Hospital
  • Sapienza University of Rome
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity


  • CD21 B cells, joint destruction, rheumatoid arthritis
Original languageEnglish
Article numbere12792
JournalScandinavian Journal of Immunology
Issue number2
Early online date2019 May 29
Publication statusPublished - 2019 Aug
Publication categoryResearch