Defective IL-10-producing B_reg cells

Credit: Macmillan Publishers Limited

IL-10-producing regulatory B (B_reg) cells are defective and exist in fewer numbers in patients with rheumatoid arthritis (RA) compared with healthy individuals, according to new research. “We have found a significantly lower number of CD19⁺CD27⁺IL-10⁺ B cells in blood samples from patients with RA with long-standing, moderately active or active disease as compared with healthy controls, and that IL-10-producing B_reg cells in RA have a significantly lower capacity to inhibit IFNγ production in autologous CD4⁺ type 1 helper T cells,” says Gabriella Sármay, corresponding author of the study.

B_reg cells have important roles in inflammation and autoimmunity, such as the regulation of T-cell responses, antigen presentation and cytokine production. B_reg cells, especially those expressing IL-10, are associated with arthritis, but their source and specific roles have remained elusive.

Previous studies have shown conflicting results regarding the involvement of IL-10-producing B_reg cells in RA. Sármay and colleagues found that IL-10 production could be efficiently induced in human B_reg cells by treatment with a combination of CpG oligodeoxynucleotide and CD40 ligand (CD40L) for 48 hours. Treating peripheral blood mononuclear cells with CpG and CD40L revealed that the percentage of IL-10-expressing cells was higher among CD19⁺CD27⁺ memory B cells than CD19⁺CD27⁻ naive B cells.

B^reg cells, especially those expressing IL-10, are associated with arthritis

Using these stimulation conditions, the researchers found that the number of CD19⁺CD27⁺IL-10⁺ B_reg cells was lower in the peripheral blood of patients with RA than in healthy individuals. In vitro, CD19⁺CD27⁺IL-10⁺ B_reg cells from patients with RA had a lower capacity to suppress IFNγ production by CD4⁺ T cells than the same cells from healthy individuals.

The addition of IL-21 to the stimulation conditions synergistically increased the number and the suppressive function of IL-10-producing B_reg cells to the same extent in patients with RA and healthy individuals. “The capacity of IL-21 to expand the IL-10-producing B_reg cell population in samples from patients with RA might indicate a possible therapeutic application for IL-21,” explains Sármay.

“We are planning to monitor proinflammatory versus suppressive cytokine expression by IL-10-producing B_reg cells and regulatory plasmablasts from patients with RA receiving biological therapies to clarify if cytokine expression by these cells has diagnostic or prognostic significance,” she concludes.