The effects of anti-idiotypic antibody on antibody production and apoptosis of anti-dsDNA antibody producing cells

Abstract

OBJECTIVE: Systemic lupus erythematosus is an autoimmune disease characterized by the production of anti-dsDNA antibody. Because the titer of anti-dsDNA antibody is correlated with disease severity, especially in lupus nephritis, controlling anti-dsDNA antibody production is important in the treatment of SLE. There are many regulatory mechanisms of autoantibody production; one of these is the interaction between idiotype and anti-idiotype antibody (anti-Id). The purpose of the present study was to assess the effect of anti-Id on anti-dsDNA antibody production and apoptosis and to study the mechanism of anti-Id induced apoptosis. METHODS: After anti-dsDNA antibody producing hybridomas were treated with anti-Id, we checked the amount of anti-dsDNA antibody production, the rate of transcription, cellular proliferation, and apoptosis. Also, after treatment with anti-oxidant (N-acetyl-Lcysteine), phorbol esters with calcium ionophore and corticosteroids, we compared their effect on apoptosis with anti-Id. RESULTS: Two types of anti-dsDNA antibody producing hybridomas (G1-2, gamma and kappa chains; M2-10, mu and kappa chains) were treated with anti-Id and it was found that: (1) the amount of anti-dsDNA antibody production decreased; (2) the rate of transcription and cellular proliferation did not decrease; and (3) the level of apoptosis increased. The two cells expressed Fas and Fas-ligand, and the Fas of G1-2 was functional but that of M2-10 was not. The treatment of these cells with anti-Id resulted in no change in Fas-ligand and Bax expression, but the expression of Bcl-2 was decreased. In addition, treatment with antioxidant (N-acetyl-L-cysteine) inhibited anti-Id-induced apoptosis in G1-2 and M2-10. Phorbol esters with calcium ionophore also inhibited anti-Id induced apoptosis in M2-10. Corticosteroids induced apoptosis in both cells and showed similar results with anti-Id induced apoptosis. CONCLUSION: The anti-Id suppressed the production of anti-dsDNA antibody in two cells by inducing apoptosis, as did prednisolone. Furthermore, Bcl-2, oxygen-free radicals and protein kinase C might be involved in the induction of apoptosis by anti-Id.