Lackofconnectivity between theinduced and autoimmune repertoires oflpr/lpr mice

SUMMARY Ithasbeenproposed thattheautoantibody-secreting cells active during autoimmune diseases are derived fromBcells initially responding toenvironmental antigens. Inorder totesttherelationship between theantigen-induced andautoimmune repertoires, we monitored thefateofantigenactivated idiotypically defined Bcells present inmicethatdeveloped thesystemic lupus erythematosus(SLE)-like syndrome associated withthelprmutation. Micehomozygous forboththeA/Jderived IghandIgKregion haplotypes andthelprmutation werebred. Immunization ofthese mice withp-azophenylarsonate (Ars)-protein conjugates elicited theidiotypic components(IdCR) characteristic oftheA/Janti-Ars responseanddidnotinterfere withthespontaneous development of thelpr-mediated autoimmune disease. TheseId/lpr miceprovided an ideal system forstudying the relationship between theexogenously andendogenously induced responsesbecause: (1)VHIdCR antibodies havebeenshowntobindautoantigens invitro; and(2)serological andmolecular reagents exist whichcan identify andmonitor VHldCRantibody production asdisease progresses. Serum samples andhybridoma celllines derived fromnon-immune as wellas Ars-keyhole limpet haemocyanin (KLH)-immunized Id/lpr miceweremonitored foridiotype expression aswell asArs andssDNAreactivity atvarious stages ofdisease progression. Wefoundthatantibodies utilizing the VHIdCR genesegmentdidnotpreferentially contribute totheautoantibody pool. Moreover, even whenIdCRB-cell clones wereexpanded bydeliberate immunization withArs-KLH, Arsnon-binding variants wereonlyrarely detected among theactivated B-cell populations ofdiseased mice. These results indicate that there isonlyminimal overlap between theVHIdCR conventional andautoimmune repertoires.