The genetic regulation of the induction of experimental SLE

We have recently reported the induction of systemic lupus erythematosus (SLE) in C3H.SW female mice by their immunization with a human monoclonal anti-DNA antibody that bears a common idiotype termed 16/6 Id. In the present study, the ability to induce experimental SLE in seven inbred mouse strains by immunization with the 16/6 Id was examined. Two out of the seven strains failed to develop the disease. These two strains did not produce antibodies specific to the 16/6 Id, while the other five strains produced high titres of anti-16/6 Id antibodies. The anti-16/6 Id antibody response, followed by the induction of the disease, was not found to be MHC or Ig heavy chain allotype linked. F₁ hybrids between a resistant strain and two of the susceptible strains were found to be resistant to the induction of the disease, indicating that susceptibility is inherited as a recessive trait. In the autoimmune NZB/W F₁ female mice, immunization with the 16/6 Id resulted in an early onset of the SLE-like disease. The results of the present study indicate the role of the anti-16/6 Id antibodies in the induction of experimental SLE, and provide direct evidence for the importance of the genetic background in determining susceptibility to SLE.