793 - Crucial Role of B Cells in Arthritis Immunized by Glucose-6-Phosphate Isomerase

Yoko Watanabe, Isao Matsumoto, Keiichi Iwanami, Aska Inoue, Mizuko Mamura, Daisuke Goto, Satoshi Ito, Akito Tsutsumi, Takayuki Sumida. Clinical Immunology, Graduate School of Comprehensive Human Science, University of Tsukuba, Tsukuba, Japan
Presentation Number: 793

[Purpose]
Glucose-6-phosphate isomerase (GPI) is a ubiquitous cytoplasmic enzyme that is recognized as an autoantigen in K/BxN mice. Anti-GPI antibodies (Abs) in K/BxN mice directly induce arthritis. Although in the other GPI-dependent model mediated by GPI immunization, transfer of serum immunoglobulins could not lead apparent arthritis. CD4+ T cell dependency was already demonstrated in this DBA/1 mice model, however the role of B cells and immunoglobulins are still mystery. To illuminate the role of B cells in this model, we used adoptive transfer of GPI immunized spleen cells to CB17/ Icr- Prkdcscid (SCID) mice.
[Method]
Male DBA/1 mice were immunized with 300μg of human recombinant GPI (rh-GPI) emulsified in CFA. 1) Splenic cells (1x107 cells) from immunized DBA/1 mice (at day14) with 100μg of rh-GPI were transferred to SCID mice (8-10 weeks of age). The severity of arthritis was assessed in donor and recipient mice using scoring system of 0-3 in each paw. Anti-GPI Ab titers were measured. 2) Splenic cells depleted CD19+ cells (1x107 cells) by MACS were transferred to SCID mice. Transferred cell population was evaluated by FACS. 3) SCID mice transferred either serum (500μl) of arthritic DBA/1 mice with CD19+ depleted splenic cells or serum alone were compared.
[Results]
1) SCID mice transferred with DBA/1 derived splenic cells were arthritic at day 5. The joint swelling of SCID mice was different from DBA/1, in terms of arthritis involvement with finger joints. In control mice (no GPI or no immunization), any arthritis was not observed. Arthritis positivity was correlated to the production of anti-GPI Abs. 2) In the case of splenic cells depleted CD19+ cells, arthritis was not found in cell transferred SCID mice. Anti-GPI Abs were not detectable. Purity of CD19+ cells was < 1.0%. 3) SCID mice transferred immunized DBA/1 serum with CD19+ depleted cells induced arthritis, although SCID mice injected with serum alone did not.
[Conclusion]
These results suggest that B cells play a crucial role in the generation of arthritis in GPI- immunized mouse model. Moreover, B cells might function as the autoantibody producer rather than the antigen presenting cells.

 Y. Watanabe, None.