Dynamics of serum IgM autoreactive repertoires following immunization: strain specificity, inheritance and association with autoimmune disease susceptibility.

Immunization of Lewis rats with myelin basic protein (MBP) in complete Freud's adjuvant (CFA) provokes experimental allergic encephalomyelitis (EAE). Here we compare, irrespective of antigen specificity, the structure and dynamics of serum IgM autoreactive repertoires following immunization with MBP/CFA in EAE-susceptible Lewis and relatively resistant Fischer rats. Prior to the appearance of clinical symptoms, Lewis rats developed a specific modification of serum IgM autoreactivities that, scored on other determinants than MBP itself, showed a prognostic association with EAE symptoms. Although comparable in their production of MBP-specific serum IgM and IgG antibodies, Fischer rats did not share these MBP/CFA-induced IgM autoreactivities of Lewis rats when immunized in the same manner. Moreover, while the Lewis-type repertoire reaction was specific for MBP/CFA alone, the respective Fischer reaction was not qualitatively different from that observed in this strain upon non-pathogenic immunization with self-related or -unrelated antigens. In general, the repertoire reactions differed qualitatively between the strains, consisting of components with typical behavior and strain preferences. The EAE-associated, as well as the other components of both Lewis- and Fischer-type repertoire reactions were usually co-dominantly inherited in F1 animals. These results indicate that a global antibody repertoire analysis may serve as a tool to describe prototypical response structures, possibly involved in immune regulation and susceptibility to pathogenic autoimmunity.