Background/Purpose:

In addition to antibodies production, B cells have
been shown to have down-regulatory function on immune response in both mouse and
human. The down-regulatory function
of B cells is partially dependent on their production of Interleukin-10 (IL-10),
an anti-inflammatory cytokine. IL10-producing B cells (B10 cells) are not
restricted to a defined population. CD24^hiCD38^hi transitional
B cells and CD24^hiCD27⁺ memory B cells have been reported
to contain the majority of B10 cells in different studies. B10 cells have been demonstrated
to ameliorate collagen-induced arthritis in mice. In human, very little is
known about the role of B10 cells in juvenile idiopathic arthritis (JIA). In this
study, we aimed to analyze the percentage and phenotypes of B10 cells in active and inactive polyarticular JIA (poly-JIA) patients and controls.

Methods:

Ten poly-JIA patients (7 active and 3 inactive) and
10 children with joint pain but without arthritis were included in this study. Inactive
disease was defined as an active joint count of 0, absence of uveitis and a Physician
Global Assessment <10 mm with normal erythrocyte sediment rate (ESR). B10
cells were generated from peripheral blood mononuclear cells stimulated with CpG and CD40L for 48 hours, and phorbol
12-myristate 13-acetate+ionomycin+brefeldin A (PIB) for the last 6 hours.
Intracellular B cell IL-10 and surface markers were assessed by flow cytometry.

Results:

The percentage of B10 cell was significantly higher
in inactive poly-JIA patients than in active patients and controls (12.83±0.50 vs.
5.05±1.31, P=0.006; 12.83±0.50 vs. 4.62±0.73,
P<0.0001), while there was no
significant difference of B10 % between active patients and controls (P=0.762)(Figure A and B). Although there
was no significant difference of the percentages of CD24^hiCD27⁺CD19⁺
B cells among the three groups (8.22±1.78 in active poly-JIA, 10.94±1.05 in
inactive poly-JIA, and 10.60±1.96 in healthy control, P=0.623), the percentage of IL10⁺CD24^hiCD27⁺CD19⁺
B cells was significantly higher in inactive patients than in active patients (1.82±0.25
vs. 0.71±0.17, P=0.007), and was similar
in active patients compared to controls (0.71±0.17 vs. 0.86±0.24, P=0.658)(Figure C). The percentages of CD24^hiCD38^hiCD19⁺
B cells and IL10⁺CD24^hiCD38^hiCD19⁺
B cells between active and inactive patients had not reached statistical difference,
but the percentage of IL10⁺CD24^hiCD38^hiCD19⁺B
cells in inactive patients was significantly higher than in controls (2.48±0.55
vs. 1.14±0.17, P=0.008)(Figure D). There
was no correlation between B10 percentage and ESR within active poly-JIA
patients.

Conclusion:

B10 cells are increased in patients whose disease
is inactive, which suggests a role of them in controlling disease activity in poly-JIA
pathogenesis. More samples and follow-up are needed to confirm these results.