title: Characterization of Regulatory B Cells in Graves' Disease and Hashimoto's Thyroiditis.
abstract: A hallmark of regulatory B cells is IL-10 production, hence their designation as IL-10+ B cells. Little is known about the ability of self-antigens to induce IL-10+ B cells in Graves' disease (GD), Hashimoto's thyroiditis (HT), or other autoimmune disease. Here we pulsed purified B cells from 12 HT patients, 12 GD patients, and 12 healthy donors with the thyroid self-antigen, thyroglobulin (TG) and added the B cells back to the remaining peripheral blood mononuclear cells (PBMCs). This procedure induced IL-10+ B-cell differentiation in GD. A similar tendency was observed in healthy donors, but not in cells from patients with HT. In GD, B cells primed with TG induced IL-10-producing CD4+ T cells. To assess the maximal frequency of inducible IL-10+ B cells in the three donor groups PBMCs were stimulated with PMA/ionomycin. The resulting IL-10+ B-cell frequency was similar in the three groups and correlated with free T3 levels in GD patients. IL-10+ B cells from both patient groups displayed CD25 or TIM-1 more frequently than did those from healthy donors. B-cell expression of two surface marker combinations previously associated with regulatory B-cell functions, CD24hiCD38hi and CD27+CD43+, did not differ between patients and healthy donors. In conclusion, our findings indicate that autoimmune thyroiditis is not associated with reduced frequency of IL-10+ B cells. These results do not rule out regulatory B-cell dysfunction, however. The observed phenotypic differences between IL-10+ B cells from patients and healthy donors are discussed.
authors.affiliation: Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
authors.forename: Birte
authors.initials: B
authors.lastname: Kristensen
authors.affiliation: Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Hegedüs
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, United States of America.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Lundy
authors.affiliation: Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Marie K
authors.initials: MK
authors.lastname: Brimnes
authors.affiliation: Department of Ophthalmology and Visual Sciences, Kellogg Eye Center and Division of Metabolism, Endocrinology, and Diabetes, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, United States of America.
authors.forename: Terry J
authors.initials: TJ
authors.lastname: Smith
authors.affiliation: Institute for Inflammation Research, Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
authors.forename: Claus H
authors.initials: CH
authors.lastname: Nielsen
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000276:immunology*; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D051927:CD24 Antigen / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006111:Graves Disease / Q000276:immunology*; D050031:Hashimoto Disease / Q000276:immunology*; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology; D008875:Middle Aged; D011991:Receptors, Virus / Q000276:immunology; D013954:Thyroglobulin / Q000276:immunology; D013961:Thyroid Gland / Q000276:immunology
chemical_list: D051927:CD24 Antigen; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; C508609:IL10 protein, human; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D016753:Interleukin-10; D013954:Thyroglobulin; D051997:ADP-ribosyl Cyclase 1