RT Journal Article
SR Electronic
T1 CD19<sup>+</sup>CD24<sup>hi</sup>CD38<sup>hi</sup> B Cells Maintain Regulatory T Cells While Limiting T<sub>H</sub>1 and T<sub>H</sub>17 Differentiation
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP 173ra23
OP 173ra23
DO 10.1126/scitranslmed.3005407
VO 5
IS 173
A1 Flores-Borja, Fabian
A1 Bosma, Anneleen
A1 Ng, Dorothy
A1 Reddy, Venkat
A1 Ehrenstein, Michael R.
A1 Isenberg, David A.
A1 Mauri, Claudia
YR 2013
UL http://stm.sciencemag.org/content/5/173/173ra23.abstract
AB 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.