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DNA Binding to Mouse Cells is Mediated by Cell-Surface Molecules: The Role of These DNA-Binding Molecules as Target Antigens in Murine Lupus

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Sharon L. McCoy

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Jane I. Morton

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Antony C. Bakke

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Kenneth A. Cornell

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Lisa E. Brown

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Robert M. Bennett

Department of Immunology, Veterans Affairs Medical Center, and Department of Medicine and Clinical Pathology, Oregon Health Sciences University, Portland, Oregon, USA

Autoimmunity to a 28-29-kDa cell-surface DNA-binding molecule has previously been described in patients with systemic lupus erythematosus and related autoimmune diseases. This report describes experiments that implicate a similar antigen-antibody system in the evolution of autoimmunity in lupus-prone mice. DNA binding to murine spleen cells was found to be a saturable phenomenon that was inhibited by excess cold DNA and trypsinization. The role of autoimmunity to murine cell-surface DNA-binding molecules in lupus-prone mice (MRL lpr/lpr, MRL + / +, BXSB) was compared to normal mice (BALB/c, C3H.SW) by means of an assay that measured the inhibition of cell-surface DNA binding. Only sera from lupus strains had inhibitory activity and this component was shown to be an IgM autoantibody. Furthermore, we isolated a spontaneously occurring IgM monoclonal antibody from the spleen of an MRL/lpr mouse, which inhibited DNA binding to mouse cells. Time-course studies indicated that young female MRL/lpr mice lacked detectable activity against cell- surface DNA-binding molecules; however, by 8-10 weeks maximal inhibitory activity was observed. This response occurred prior to the development of significant antinuclear antibody activity. With the appearance of overt disease and anti-DNA antibodies, inhibition of DNA- binding activity became undetectable. These findings mirror previous studies on autoimmunity to a cell-surface DNA-binding molecule on human leucocytes, but have the added advantage of permitting the study of the temporal evolution of this inhibitory activity in relation to disease expression.

Key Words: Cell-surface • DNA-binding molecules • Lupus

Lupus, Vol. 1, No. 3, 167-173 (1992)
DOI: 10.1177/096120339200100308


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