Lupus-like syndrome in some strains of nude mice

Nude mice (strains ORL, C57BL, BALB/C), as well as neonatally thymectomized mice, develop spontaneous antinuclear antibodies (ANab) and antidouble-stranded DNA antibodies (dsDNAab). Later, these animals develop a lupus-like syndrome in which immunoglobulin (Ig) deposits appear, first in the kidney glomeruli, then at the dermoepidermal junction and in the choroid plexus. In the beginning, these Ig are IgM and IgG2; later, IgG1 and IgA deposit in the kidneys. The classes of the Ig of the deposits correspond to those of the circulating ANab-Ig, except for IgA. Acid eluates from kidneys and skin, contain anti-DNA histone ab. An increased C1q binding activity is observed in 8- to 12-wk-old ORL nude mice with ANab, but is not observed in age-matched ORL nude mice without ANab. These data indicate the participation of ANab in the constitution of immune complexes and of tissular Ig deposits in nude mice. The antinuclear autoimmunization process, in nude as well as in thymectomized mice, might be interpreted as a defect of T suppressor cells, which normally control autoimmune clones. However, in contrast with the preceding strains of nude mice, nude mice from the IFFA centre, which have a different genetic background, develop neither ANab, nor dsDNAab, nor glomerular lesions. Three hypotheses can be proposed to explain these particularities of IFFA nude mice. They either have an immune response regulating system, independent of the thymus which is defective or absent in the other strains, or they are deprived of lymphocytes able to produce ANab and dsDNAab, or there are not enough free nuclear antigens to stimulate an immune response. Preliminary results obtained in our laboratory favour the first hypothesis.