b cell depletion reduces the number of autoreactive t helper cells and prevents glucose-6-phosphate isomerase-induced arthritisb细胞消耗减少了autoreactive t辅助细胞的数量,防止glucose-6-phosphate isomerase-induced关节炎.pdf

B Cell Depletion Reduces the Number of Autoreactive T Helper Cells and Prevents Glucose-6-Phosphate Isomerase-Induced Arthritis 1,2. 1. 3 4 1 Oliver Frey , Lisa Bruns , Lars Morawietz , Kyri Dunussi-Joannopoulos , Thomas Kamradt * 1 Institute of Immunology, Jena University Hospital, Jena, Germany, 2 Institute of Clinical Chemistry and Laboratory Diagnostics, Jena University Hospital, Jena, Germany, ´ 3 Institut of Pathology, Charite University Hospital Berlin, Berlin, Germany, 4 Pfizer Research, Cambridge, Massachusetts, United States of America 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 a