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.