title: Etanercept attenuates collagen-induced arthritis by modulating the association between BAFFR expression and the production of splenic memory B cells.
abstract: Anti-tumour necrosis factor-α (TNF-α) drugs are approved for the treatment of rheumatoid arthritis (RA). Many studies have investigated the effect of these drugs on the T cell response; however, some clues have indicated that it may also target B cells. This study was carried out to explore the potential effects and mechanisms of etanercept, a soluble TNF-α receptor, on the function of B cells and their development into memory B cells in type II collagen (CII)-induced arthritis (CIA). Beginning on day 24 after CII immunisation, the mice were evaluated every 2-3 days to determine two clinical parameters: their arthritis global assessment and swollen joint count (SJC). The serum concentrations of IgG1, IgG2a and anti-CII antibodies and the splenic pathology and proliferation of B cells were measured. The percentage of total memory B cells in the spleen was analysed with flow cytometry. BAFFR was detected by immunohistochemistry. In CIA mice, etanercept markedly suppressed the arthritis global assessment and the SJC, reduced the production of anti-CII, IgG1 and IgG2a antibodies, and prevented spleen histopathology to varying degrees; however, it had no obvious effect on splenic B cell proliferation. Etanercept also decreased the percentage of total CD27(+) memory B cells in the spleen. Treatment with etanercept was associated with a further increase in BAFFR expression, a significant reduction in CD27 expression, and a negative correlation between the levels of BAFFR and the percentage of memory B cells. Our findings showed that increased BAFFR expression has a regulatory effect on the activation of B cells and the generation of memory B cells, which may be one of the mechanisms of the therapeutic effects of etanercept.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Hefei 230032, Anhui Province, PR China. hfwqt727@163.com
authors.forename: Qing-Tong
authors.initials: QT
authors.lastname: Wang
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Wu
authors.forename: Bei
authors.initials: B
authors.lastname: Huang
authors.forename: Yu-Kun
authors.initials: YK
authors.lastname: Ma
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Song
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Zhang
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Chen
authors.forename: Hua-Xun
authors.initials: HX
authors.lastname: Wu
authors.forename: Wu-Yi
authors.initials: WY
authors.lastname: Sun
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D053265:B-Cell Activation Factor Receptor / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D024043:Collagen Type II / Q000276:immunology; D000068800:Etanercept; D007074:Immunoglobulin G / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D007156:Immunologic Memory; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000276:immunology
chemical_list: D018501:Antirheumatic Agents; D053265:B-Cell Activation Factor Receptor; D024043:Collagen Type II; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; C486662:Tnfrsf13c protein, mouse; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D000068800:Etanercept