title: CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation.
abstract: 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(+)CD24(hi)CD38(hi) 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(+)CD24(hi)CD38(hi) B cells. Healthy CD19(+)CD24(hi)CD38(hi) B cells inhibited naïve T cell differentiation into T helper 1 (T(H)1) and T(H)17 cells and converted CD4(+)CD25(-) T cells into regulatory T cells (T(regs)), in part through the production of IL-10. In contrast, CD19(+)CD24(hi)CD38(hi) B cells from patients with rheumatoid arthritis (RA) failed to convert CD4(+)CD25(-) T cells into functionally suppressive T(regs) or to curb T(H)17 development; however, they maintained the capacity to inhibit T(H)1 cell differentiation. Moreover, RA patients with active disease have reduced numbers of CD19(+)CD24(hi)CD38(hi) 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(+)CD24(hi)CD38(hi) B cells with regulatory function may fail to prevent the development of autoreactive responses and inflammation, leading to autoimmunity.
authors: Centre for Rheumatology, Division of Medicine, University College London, 5 University Street, London WC1E 6JF, UK.
authors: Fabian
authors: F
authors: Flores-Borja
authors: Anneleen
authors: A
authors: Bosma
authors: Dorothy
authors: D
authors: Ng
authors: Venkat
authors: V
authors: Reddy
authors: Michael R
authors: MR
authors: Ehrenstein
authors: David A
authors: DA
authors: Isenberg
authors: Claudia
authors: C
authors: Mauri
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018941:Antigens, CD19 / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D051927:CD24 Antigen / Q000276:immunology*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D051927:CD24 Antigen; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051997:ADP-ribosyl Cyclase 1