Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies.
Antibodies against the N-terminal (NT) but not the basic domain (BD), DNA binding regions of the largest subunit (S1) of RNA polymerase I (RNAPI) were detected in the sera of MRL-lpr/lpr lupus mice. Antibodies against both RNAPI(S1)-NT and -BD, as well as other systemic lupus erythematosus (SLE) autoantigens (La, ribosomal P proteins and Sm/RNP) were produced by rabbits immunized with anti-DNA antibodies that had been affinity purified from SLE patients. Immunization of nonautoimmune mice (Balb/c) with RNAPI(S1)-NT, RNAPI(S1)-BD, or La in the form of GST fusion proteins, induced production of anti-double-stranded (ds) DNA and anti-Sm/RNP. GST-P1 did not induce an anti-dsDNA response in these mice. These results demonstrate that RNAPI(S1)-NT, RNAPI(S1)-BD and La can participate in an anti-autoantigen/anti-DNA antibody loop during an SLE-like autoimmune response.
Sciascia
Sandra A
SA
Department of Molecular Biosciences, University of Kansas. Lawrence, KS 66045, USA.
Robson
Kristina
K
Zhu
Liangjin
L
Garland
Michael
M
Grabosch
Shannon
S
Kelamis
Joseph
J
Messamore
Will
W
Bradley
Todd
T
Sourk
Allison
A
Westberg
Lindsey
L
Goodnight
Waco
W
Tongson
Krystina
K
Holloway
Naomi
N
Wardak
Zabi
Z
Sudyka
Michelle
M
Masrani
Shriti
S
Chintalapati
Sanket
S
Cagaanan
Manuel
M
Brown
John C
JC
Stetler
Dean A
DA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis* / Q000276:immunology; D001324:Autoantigens / Q000096:biosynthesis / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D005260:Female; D007114:Immunization; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D017434:Protein Structure, Tertiary; D012318:RNA Polymerase I / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D012261:Ribonucleoproteins / Q000096:biosynthesis / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000096:biosynthesis / Q000276:immunology*; D055517:snRNP Core Proteins; D000097585:SS-B Antigen
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D012318:RNA Polymerase I; D012261:Ribonucleoproteins; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D000097585:SS-B Antigen