CD19(+)CD24(hi)CD38(hi) B Cells Maintain Regulatory T Cells While Limiting T(H)1 and T(H)17 Differentiation
Volume
5
Publisher
DOI
10.1126/scitranslmed.3005407
Journal
SCIENCE TRANSLATIONAL MEDICINE
Issue
ISSN
1946-6234
Metadata
Show full item recordAbstract
The relevance of regulatory B cells in the maintenance of tolerance in healthy individuals or in patients with immune disorders remains understudied. In healthy individuals, CD19+
CD24hiCD38hi B cells suppress CD4+
CD25− T cell
proliferation as well as the release of interferon-g and tumor necrosis factor–a by these cells; this suppression is
partially mediated through the production of interleukin-10 (IL-10). We further elucidate the mechanisms of
suppression by CD19+
CD24hiCD38hi B cells. Healthy CD19+
CD24hiCD38hi B cells inhibited naïve T cell differentiation into T helper 1 (TH1) and TH17 cells and converted CD4+
CD25− T cells into regulatory T cells (Tregs),
in part through the production of IL-10. In contrast, CD19+
CD24hiCD38hi B cells from patients with rheumatoid
arthritis (RA) failed to convert CD4+
CD25− T cells into functionally suppressive Tregs or to curb TH17 development;
however, they maintained the capacity to inhibit TH1 cell differentiation. Moreover, RA patients with active disease have reduced numbers of CD19+
CD24hiCD38hi B cells in peripheral blood compared with either patients with
inactive disease or healthy individuals. These results suggest that in patients with active RA, CD19+
CD24hiCD38hi
B cells with regulatory function may fail to prevent the development of autoreactive responses and inflammation,
leading to autoimmunity.