Development of functional B cells in a line of SCID mice with transgenes coding for anti-double-stranded DNA antibody

Deletion or inactivation of anti-self (DNA) B cells has been reported in non-autoimmune mice bearing Ig transgenes that code for Abs with specificity for dsDNA or ssDNA. However, we report a case in which anti-dsDNA B cells appear to escape both deletion and inactivation. We show that B cells (B220(+)IgM(+)) can develop in non-autoimmune SCID mice bearing two site-directed transgenes, 3H9(56R) and V kappa 8, that together code for an anti-dsDNA Ab. The B cells appear inactive, because the mice (56RV kappa 8 SCID mice) generally lack serum Ig. However, 56RV kappa 8 SCID mice are able to produce IgG Ab with specificity for dsDNA when they become "leaky" for T cells or are reconstituted with exogenous T cells from B cell-deficient JH(-/-) donors. Thus, anti-dsDNA B cells that escape deletion in 56RV kappa 8 SCID mice appear fully functional and can differentiate, class switch, and give rise to IgG-producing cells in the presence of T cells and self-Ag.