Significant association between the skewed natural antibody repertoire of Xid mice and resistance to Trypanosoma cruzi infection

The Xid mutation predominantly affects the development of B cells and conse quently the levels and composition of natural antibodies in sera. In contra st to the congenic and susceptible BALB/c strain, immunodeficient BALB.Xid mice display a resistant phenotype both to acute Trypanosoma cruzi infectio n and to the development of severe cardiopathy. Because natural antibodies are known to be basically self-antigen driven, IgM and IgG natural antibody repertoires (NAR) were compared before and during infection in these two s trains. The analysis revealed fundamental alterations of IgM and IgG NAR in pre- and post-infected Xid mice. In particular, relatively increased natur al (pre-existing) autoreactive IgG, dominated by the unique recognition of a single band in autologous heart extracts, was typical for uninfected Xid mice. This natural autoreactive IgG directed to heart antigens disappeared early after infection not only in Xid, but also in individual BALB/c mice t hat survived the acute infection. Conversely, the subgroup of BALB/c mice t hat died early after infection presented the most pronounced instances of t he rapid, relative increase of IgM reactivities to self and non-self protei ns. These results suggest that self-reactive NAR may play a role in an immu noregulatory mechanism relevant for the determination of susceptibility/res istance to infections. This may act either by influencing specific response s, or by modulating the self-aggressive components responsible for patholog y.