Induction of pathogenic anti-dsDNA antibodies is controlled on the level of B cells in a non-lupus prone mouse strain.
The SmD1(83-119) peptide is a main target of autoantibodies and T cells in human and murine lupus, but its role in autoimmunity induction remains elusive. Therefore, female Balb/c mice and (NZW x Balb/c)F1 [CWF1] mice with identical MHC haplotype as lupus prone NZB/W mice were immunized with SmD1(83-119). Immunizations of CWF1 mice with SmD1(83-119), but not with the controls (irrelevant peptide, HEL peptide, or saline), induced anti-SmD1(83-119) and anti-dsDNA antibodies and proteinuria not present in Balb/c mice. DsDNA-specific plasma cell induction after SmD1(83-119) immunizations was confirmed by ELISPOT assays showing that the generation of dsDNA-specific antibody forming cells (AFC) was mainly driven by increased T-cell help. T-cell help for the generation of dsDNA-specific AFC was also present in saline-treated CWF1 mice but was controlled on the levels of B cells preventing autoimmunity.
Langnickel
Dirk
D
Department of Rheumatology and Clinical Immunology, Charité University Hospital, Humboldt University of Berlin, Berlin, Germany.
Enghard
Philipp
P
Klein
Claudia
C
Undeutsch
Reinmar
R
Hocher
Berthold
B
Manz
R
R
Burmester
G R
GR
Riemekasten
Gabriela
G
D000818:Animals; D000974:Antibodies, Antinuclear / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D005260:Female; D007114:Immunization; D008177:Lupus Vulgaris / Q000235:genetics* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008814:Mice, Inbred NZB; D010446:Peptide Fragments / Q000276:immunology; D017411:Ribonucleoproteins, Small Nuclear / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D055517:snRNP Core Proteins
D000974:Antibodies, Antinuclear; D010446:Peptide Fragments; D017411:Ribonucleoproteins, Small Nuclear; C489793:Snrpd1 protein, mouse; D055517:snRNP Core Proteins; D004247:DNA