We read the interesting article by Hamel et al. (1), which provides encouraging data on the role of B cells in arthritis. We suggest that increasing T regulatory cells (Tregs) reveals a novel mechanism of B cell depletion in rheumatoid arthritis (RA) therapy.

B cells play a pivotal role in the pathogenesis of RA through autoantibody production, chemokine/cytokine secretion, and inhibiting autoreactive T cell responses (2). Although a series of treatment regimens that affect B cells was developed (3), the exact mechanism for the efficacy of B cell-depletion therapy remains unclear. The depletion of B cells with a decrease in autoantibodies in RA does not necessarily correlate with the clinical outcome, indicating that mechanisms other than producing Abs are in operation. Recently, Yeo et al. (4) identified B cells as the main source of receptor activator of NF-κB ligand, which contributes to osteoclast activation and bone destruction. Interestingly, Hamel et al. (1) first correlated B cell depletion with the improvement of Tregs, which can inhibit osteoclast formation and activation (5), and with other regulatory mechanisms. The authors found that during proteoglycan-induced arthritis (PGIA), B cell depletion strikingly increased Tregs and decreased the severity of arthritis. In addition, both Tregs and B cell depletion restored proteoglycan-induced arthritis, although the resurgent autoantibody response was absent.

Collectively, B cell depletion could be used for controlling arthritis by improving Tregs. Better insights into the role of B cell depletion in Treg-mediated osteoclast suppression could result in innovative therapies for RA and other bone-destructive diseases.

1
Hamel
K. M.
,
Cao
Y.
,
Ashaye
S.
,
Wang
Y.
,
Dunn
R.
,
Kehry
M. R.
,
Glant
T. T.
,
Finnegan
A.
.
2011
.
B cell depletion enhances T regulatory cell activity essential in the suppression of arthritis
.
J. Immunol.
187
:
4900
4906
.
2
Hamel
K.
,
Doodes
P.
,
Cao
Y.
,
Wang
Y.
,
Martinson
J.
,
Dunn
R.
,
Kehry
M. R.
,
Farkas
B.
,
Finnegan
A.
.
2008
.
Suppression of proteoglycan-induced arthritis by anti-CD20 B Cell depletion therapy is mediated by reduction in autoantibodies and CD4+ T cell reactivity
.
J. Immunol.
180
:
4994
5003
.
3
Nakken
B.
,
Munthe
L. A.
,
Konttinen
Y. T.
,
Sandberg
A. K.
,
Szekanecz
Z.
,
Alex
P.
,
Szodoray
P.
.
2011
.
B-cells and their targeting in rheumatoid arthritis - Current concepts and future perspectives
.
Autoimmun. Rev.
11
:
28
34
.
4
Yeo
L.
,
Toellner
K. M.
,
Salmon
M.
,
Filer
A.
,
Buckley
C. D.
,
Raza
K.
,
Scheel-Toellner
D.
.
2011
.
Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis
.
Ann. Rheum. Dis.
70
:
2022
2028
.
5
Zaiss
M. M.
,
Frey
B.
,
Hess
A.
,
Zwerina
J.
,
Luther
J.
,
Nimmerjahn
F.
,
Engelke
K.
,
Kollias
G.
,
Hünig
T.
,
Schett
G.
, et al
.
2010
.
Regulatory T cells protect from local and systemic bone destruction in arthritis
.
J. Immunol.
184
:
7238
7246
.