DNA binding to mouse cells is mediated by cell-surface molecules: the role of these DNA-binding molecules as target antigens in murine lupus.
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.
Hefeneider
S H
SH
Department of Immunology, Veterans Affairs Medical Center, Portland, Oregon 97201.
McCoy
S L
SL
Morton
J I
JI
Bakke
A C
AC
Cornell
K A
KA
Brown
L E
LE
Bennett
R M
RM
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis; D001324:Autoantigens / Q000378:metabolism*; D015551:Autoimmunity; D001665:Binding Sites; D001667:Binding, Competitive; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D004247:DNA / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D007075:Immunoglobulin M / Q000302:isolation & purification / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D007075:Immunoglobulin M; D004247:DNA