Effects of polyclonal immune stimulators upon NZB.<i>xid</i> congenic mice.

Abstract

Abstract The failure of congenic NZB.xid mice to produce the autoantibodies characteristic of NZB mice provided us with the opportunity to study the effects of the chronic administration of polyclonal B cell activators, poly rI•rC and LPS, on these congenic mice. We found that poly rI•rC induced the early onset of erythrocyte autoantibodies in NZB.xid mice. Congenic DBA/2.xid mice did not develop such autoantibodies. Young NZB.xid mice were more severely affected by chronic poly rI•rC injections than were older mice. Females had high titers of anti-RBC autoantibodies 3 mo after the injections had been stopped, whereas males did not. Chronic LPS administration led to the production of antibodies to RBC, thymocytes, and ssDNA in NZB.xid mice. The development of these antibodies was somewhat slower than with poly rI•rC injections. Whereas the early induction of anti-RBC and anti-ssDNA by poly rI•rC in NZB.xid mice was found to be thymic dependent (it did not occur in injected neonatally thymectomized NZB.xid mice), the later autoantibody production was thymic independent. In fact, in the absence of either poly rI•rC or LPS, neonatally thymectomized NZB.xid mice did not spontaneously produce anti-RBC antibodies at 3 mo of age (a time at which poly rI•rC-induced antibodies were present), but they did at 9 mo of age (at which time unmanipulated mice did not produce such antibodies). The induction of autoantibodies in NZB.xid mice at 9 mo of age in association with either LPS or thymectomy or both revealed that different autoantibodies could be induced by different immune manipulations. This is consistent with the demonstration that different genes control the expression of different autoantibodies and that they can be induced to be differentially expressed by varying immune manipulations. Taken together, these studies help to explain the interactions among genetic, immune, and environmental factors in the pathogenesis of autoimmunity. They also shed light upon the further interrelated factors of sex and age.