title: CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients.
abstract: The immunosuppressive function of regulatory B cells has been shown in several murine models of chronic inflammation, including collagen-induced arthritis, inflammatory bowel disease, and experimental autoimmune encephalomyelitis. Despite interest in these cells, their relevance to the maintenance of peripheral tolerance in humans remains elusive. Here, we demonstrate that human CD19(+)CD24(hi)CD38(hi) B cells possessed regulatory capacity. After CD40 stimulation, CD19(+)CD24(hi)CD38(hi) B cells suppressed the differentiation of T helper 1 cells, partially via the provision of interleukin-10 (IL-10), but not transforming growth factor-beta (TGF-beta), and their suppressive capacity was reversed by the addition of CD80 and CD86 mAbs. In addition, CD19(+)CD24(hi)CD38(hi) SLE B cells isolated from the peripheral blood of systemic lupus erythematosus (SLE) patients were refractory to further CD40 stimulation, produced less IL-10, and lacked the suppressive capacity of their healthy counterparts. Altered cellular function within this compartment may impact effector immune responses in SLE and other autoimmune disorders.
authors.affiliation: Centre for Rheumatology Research, Department of Medicine, University College London, 46 Cleveland Street, London W1T4 JF, UK.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Blair
authors.forename: Lina Yassin
authors.initials: LY
authors.lastname: Noreña
authors.forename: Fabian
authors.initials: F
authors.lastname: Flores-Borja
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawlings
authors.forename: David A
authors.initials: DA
authors.lastname: Isenberg
authors.forename: Michael R
authors.initials: MR
authors.lastname: Ehrenstein
authors.forename: Claudia
authors.initials: C
authors.lastname: Mauri
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D018941:Antigens, CD19 / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D051927:CD24 Antigen / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015398:Signal Transduction / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D051927:CD24 Antigen; D016207:Cytokines; D051997:ADP-ribosyl Cyclase 1