CD21(-/low) B cells associate with joint damage in rheumatoid arthritis patients

• 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) CD27(-)IgD(-) 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 CD27(-)IgD(-), and a third of those expressed the pro-osteoclastogenic factor receptor activator of the nuclear factor kappa B 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 CD27(-)IgD(-) subset of CD21(-/low) B cells may mediate joint destruction in patients with ACPA(+)/RF+ RA.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Immunology in the medical area (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)

Nyckelord

CD21(-)

low B cells

joint destruction

rheumatoid arthritis

marginal zone-like

peripheral-blood

population

expansion

contain

health

compartment

expression

subsets

predict

Immunology

evoo mll

1995

arthritis and rheumatism

v38

p44

CD21 B cells

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)