B cells play a crucial role as antigen-presenting cells and collaborate with inflammatory cytokines in glucose-6-phosphate isomerase-induced arthritis.
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.
Tanaka-Watanabe
Y
Y
Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tennodai, Tsukuba, Japan.
Matsumoto
I
I
Iwanami
K
K
Inoue
A
A
Goto
D
D
Ito
S
S
Tsutsumi
A
A
Sumida
T
T
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D018941:Antigens, CD19 / Q000032:analysis; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology*; D039481:CD11b Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology*; D005956:Glucose-6-Phosphate Isomerase; D015850:Interleukin-6 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D016513:Mice, SCID; D013154:Spleen / Q000276:immunology / Q000637:transplantation; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018941:Antigens, CD19; D039481:CD11b Antigen; D016207:Cytokines; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D005956:Glucose-6-Phosphate Isomerase