Lack of connectivity between the induced and autoimmune repertoires of lpr/lpr mice.
It has been proposed that the autoantibody-secreting cells active during autoimmune diseases are derived from B cells initially responding to environmental antigens. In order to test the relationship between the antigen-induced and autoimmune repertoires, we monitored the fate of antigen-activated idiotypically defined B cells present in mice that developed the systemic lupus erythematosus (SLE)-like syndrome associated with the lpr mutation. Mice homozygous for both the A/J-derived Igh and Ig kappa region haplotypes and the lpr mutation were bred. Immunization of these mice with p-azophenylarsonate (Ars)-protein conjugates elicited the idiotypic components (IdCR) characteristic of the A/J anti-Ars response and did not interfere with the spontaneous development of the lpr-mediated autoimmune disease. These Id/lpr mice provided an ideal system for studying the relationship between the exogenously and endogenously induced responses because: (1) VHIdCR antibodies have been shown to bind autoantigens in vitro; and (2) serological and molecular reagents exist which can identify and monitor VHIdCR antibody production as disease progresses. Serum samples and hybridoma cell lines derived from non-immune as well as Ars-keyhole limpet haemocyanin (KLH)-immunized Id/lpr mice were monitored for idiotype expression as well as Ars and ssDNA reactivity at various stages of disease progression. We found that antibodies utilizing the VHIdCR gene segment did not preferentially contribute to the autoantibody pool. Moreover, even when IdCR B-cell clones were expanded by deliberate immunization with Ars-KLH, Ars non-binding variants were only rarely detected among the activated B-cell populations of diseased mice. These results indicate that there is only minimal overlap between the VHIdCR conventional and autoimmune repertoires.
Very
D L
DL
Department of Microbiology, Boston University School of Medicine, Massachusetts 02118.
Panka
D J
DJ
Weissman
D
D
Wysocki
L
L
Manser
T
T
Marshak-Rothstein
A
A
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000276:immunology*; D003429:Cross Reactions / Q000276:immunology; D004277:DNA, Single-Stranded / Q000378:metabolism; D004587:Electrophoresis, Agar Gel; D006825:Hybridomas / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism; D007130:Immunoglobulin Idiotypes / Q000378:metabolism; D007075:Immunoglobulin M / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D010132:p-Azobenzenearsonate / Q000276:immunology
D001323:Autoantibodies; D004277:DNA, Single-Stranded; D007074:Immunoglobulin G; D007130:Immunoglobulin Idiotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; D010132:p-Azobenzenearsonate