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

C.H. Lee, C.H. Suh, J. Lee, Y.T. Kim1, S.K. Lee

Division of Rheumatology, Department of Internal Medicine, Institute for Immunology and Immunological Disease, BK 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul; 1Department of Microbiology, Ajou University College of Medicine, Suwon, Korea.

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, g and k chains; M2-10, m and k 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.

Key words
Anti-dsDNA antibody, anti-idiotypic antibody, apoptosis, corticosteroid.

Please address correspondence and reprint requests to: Dr. Soo-Kon Lee, Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul, Korea. 
E-mail: sookonlee@yumc.yonsei.ac.kr

Clin Exp Rheumatol 2003; 21: 291-300.
© Copyright Clinical and Experimental Rheumatology 2003.

Abbreviations: SLE: systemic lupus erythematosus; anti-Id: anti-idiotypic antibody; BCR: B cell receptor; Ig: immuno-globulin; FasL: Fas ligand; CS: corticosteroids; PARP: poly (ADP- ribose) polymerase.