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B Cell–Specific Expression of Inducible Costimulator Ligand Is Necessary for the Induction of Arthritis in Mice
Author(s) -
Hamel Keith M.,
Cao Yanxia,
Olalekan Susan A.,
Finnegan Alison
Publication year - 2014
Publication title -
arthritis and rheumatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.106
H-Index - 314
eISSN - 2326-5205
pISSN - 2326-5191
DOI - 10.1002/art.38207
Subject(s) - germinal center , cytokine , arthritis , t cell , immunology , antibody , cell , chemistry , medicine , microbiology and biotechnology , b cell , cancer research , biology , immune system , biochemistry
Objective Inducible costimulator (ICOS)–ICOSL interactions are necessary for activation of Teff cells and follicular helper T (Tfh) cells. ICOSL is expressed on B cells, macrophages, and dendritic cells and can be induced on nonhematopoietic cells. The aim of this study was to determine whether expression of ICOSL on B cells is necessary for the development of proteoglycan (PG)–induced arthritis (PGIA). Methods PGIA was initiated by immunizing wild‐type and ICOSL‐deficient (ICOSL −/− ) or B cell–specific ICOSL −/− chimeric BALB/c mice with human PG in adjuvant. The onset and severity of arthritis were monitored over time. CD4+ T cell proliferation and CD4+ T cell cytokine production were measured in vitro after the cells were restimulated with PG. Germinal center (GC) B cells, plasma cells, Tfh cells, and Treg cells were identified by staining with specific antibodies. Results Arthritis progression was completely inhibited in both ICOSL −/− mice and B cell–specific ICOSL −/− chimeric mice. Production of the Teff cell–produced cytokines interferon‐γ and interleukin‐17 (IL‐17) and the antiinflammatory cytokine IL‐4 was suppressed. The reduced percentages of GCs and Tfh cells and the decreased production of IL‐21 correlated with a decrease in the anti‐mouse PG antibody response. However, the percentage of plasma cells was not reduced despite a reduction in IgG responses. Conclusion These data indicate that the signals provided by ICOSL‐expressing B cells to Teff cells and Tfh cells are necessary for the development of arthritis. Thus, therapeutic blockade of ICOSL−ICOS interactions may be an effective strategy for the treatment of rheumatoid arthritis.