title: B cell depletion reduces the number of autoreactive T helper cells and prevents glucose-6-phosphate isomerase-induced arthritis.
abstract: The therapeutic benefit of B cell depletion in patients with rheumatoid arthritis has provided proof of concept that B cells are relevant for the pathogenesis of arthritis. It remains unknown which B cell effector functions contribute to the induction or chronification of arthritis. We studied the clinical and immunological effects of B cell depletion in glucose-6-phosphate isomerase-induced arthritis. We targeted CD22 to deplete B cells. Mice were depleted of B cells before or after immunization with glucose-6-phosphate isomerase (G6PI). The clinical and histological effects were studied. G6PI-specific antibody responses were measured by ELISA. G6PI-specific T helper (Th) cell responses were assayed by polychromatic flow cytometry. B cell depletion prior to G6PI-immunization prevented arthritis. B cell depletion after immunization ameliorated arthritis, whereas B cell depletion in arthritic mice was ineffective. Transfer of antibodies from arthritic mice into B cell depleted recipients did not reconstitute arthritis. B cell depleted mice harbored much fewer G6PI-specific Th cells than control animals. B cell depletion prevents but does not cure G6PI-induced arthritis. Arthritis prevention upon B cell depletion is associated with a drastic reduction in the number of G6PI-specific effector Th cells.
authors.affiliation: Institute of Immunology, Jena University Hospital, Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Frey
authors.forename: Lisa
authors.initials: L
authors.lastname: Bruns
authors.forename: Lars
authors.initials: L
authors.lastname: Morawietz
authors.forename: Kyri
authors.initials: K
authors.lastname: Dunussi-Joannopoulos
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
mesh_terms: D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001168:Arthritis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology*; D051379:Mice
chemical_list: D005956:Glucose-6-Phosphate Isomerase