Induction of severe autoimmune disease in normal mice by simultaneous action of multiple immunostimulators

Either of two immunostimulating factors (lpr, lipopolysaccharide) enhanced the pathogenic autoimmune responses of MRL/n mice, but the serologic and immunopathologic characteristics differed. In contrast, either factor acting alone, caused minimal immunopathology in normal mice, despite autoantibody induction. Combined immunostimulation, however, caused fatal glomerulonephritis in normal-background C57BL/6 mice. These results show the profound influence of the background genome on the effects of immunostimulating agents, and show that resistance to autoimmune disease in immunologically normal mice is not absolute.