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Clin Exp Immunol ; 155(2): 285-94, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19032549

ABSTRACT

Anti-glucose-6-phosphate isomerase (GPI) antibodies from K/BxN mice directly induce arthritis; however, the transfer of these antibodies from mice with GPI-induced arthritis does not induce arthritis. CD4(+) T cells play an important role in the induction and effector phase in this model; however, the roles of B cells and immunoglobulins (Igs) have not been elucidated. We investigated the roles of B cells and Igs in GPI-induced arthritis by using adoptive transfer system into SCID mice. Transfer of splenocytes of male DBA/1 mice immunized with GPI into SCID mice induced arthritis on day 6 in the latter, in association with the production of anti-GPI antibodies. Co-localization of C3 and IgG on the articular surface was identified in arthritic SCID mice. Inoculation of IgG (or anti-GPI antibodies) and CD19(+)-depleted splenocytes from arthritic DBA/1 mice induced arthritis in SCID mice, but not CD19(+)-depleted or CD4(+)-depleted splenocytes from DBA/1 mice. In vitro analysis of cytokine production by splenocytes from DBA/1 arthritic mice demonstrated production of large amounts of tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 in an antigen-specific manner (P < 0.01), and production was dominated by CD19(+)-depleted than CD4(+)-depleted splenocytes (P < 0.05). Addition of IgG from DBA/1 arthritic mice to the culture enhanced TNF-alpha but not IL-6 production, and this effect was blocked by anti-Fcgamma receptor antibody. In vivo analysis of neutralization with TNF-alpha protected arthritis completely in SCID mice. Our results highlight the important role of B cells in GPI-induced arthritis as autoantibody producers, and these autoantibodies can trigger joint inflammation in orchestration with inflammatory cytokines, especially TNF-alpha.


Subject(s)
Antigen Presentation/immunology , Arthritis, Experimental/immunology , B-Lymphocytes/immunology , Cytokines/immunology , Animals , Antigens, CD19/analysis , Arthritis, Experimental/chemically induced , Arthritis, Experimental/pathology , CD11b Antigen/analysis , CD4-Positive T-Lymphocytes/immunology , Cell Communication/immunology , Cells, Cultured , Coculture Techniques , Glucose-6-Phosphate Isomerase , Interleukin-6/biosynthesis , Male , Mice , Mice, Inbred DBA , Mice, SCID , Spleen/immunology , Spleen/transplantation , Tumor Necrosis Factor-alpha/biosynthesis
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