Research ArticleImmunology

CD19+CD24hiCD38hi B Cells Maintain Regulatory T Cells While Limiting TH1 and TH17 Differentiation

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Science Translational Medicine  20 Feb 2013:
Vol. 5, Issue 173, pp. 173ra23
DOI: 10.1126/scitranslmed.3005407

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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-γ and tumor necrosis factor–α 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.

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