Cross-Reactivity of Murine Monoclonal Anti-DNA Antibodies with Human and Murine Skin: A Possible Pathogenetic Role in Skin Lesions of Lupus Erythematosus

Abstract

Anti-DNA autoantibodies are known to cross-react with a wide variety of substances including cell-surface molecules. Thus, we examined cross-reactivities of 20 murine monoclonal anti-DNA antibodies with normal human and mouse skin tissues. Hybridomas producing these monoclonal antibodies were established from non-immunized spleen cells from autoimmune MRL-lpr/lpr mice, a strain characterized by spontaneous development of SLE-like disorders including skin changes. They were selected based on their reactivity to DNA in a typical enzyme-linked immunosorbent assay, in which nine monoclonal antibodies were reactive with both double-stranded DNA and single-stranded DNA, whereas nine monoclonals were reactive only with single-stranded DNA. Even though only seven of them were observed to stain nuclei, most of the monoclonal antibodies revealed strong and distinct cross-reactivities to various components of the skin tissues including the epidermal basement membrane, keratinocytes at different locations of the epidermis, melanocytes, Langerhans cells, Thy-1+ dendritic cells in the case of murine skin, and mast cells. Our results suggest a possible role of so-called anti-DNA antibodies with high or low affinities to DNA in the pathogenesis of cutaneous lesions of lupus erythematosus.