Abstract Self antigen-bearing follicular dendritic cells (FDCs) appear to be involved in the pathogenesis of autoimmunity, and interfering with the development of FDC-reticula attenuates ectopic germinal centers (GCs) & auto-Ab production. FDCs multimerize monomeric antigens in immune complexes (ICs) and present them polyvalently in an array that extensively cross-links BCRs and induces T cell independent Ig responses with FDC-BAFF & -C4bBP providing co-signals. We hypothesized that self antigens presented as multimerized ICs on FDCs would break B cell tolerance and that would be indicated by induction of autoreactive GCs & auto-Ab responses. To test this, mice were challenged with murine TNF-α or IgE in the form of ICs. Sera were assessed for auto-Ab production, and draining lymph nodes were examined for autoreactive GCs and plasma cells. Murine TNF-α & IgE ICs were retained on well-developed FDC reticula and numerous GCs & plasma cells were induced. Murine TNF-α & IgE-specific IgM auto-Abs were detectable in 48 hrs, and switched to IgG by day 6. This is the first report indicating that B cell tolerance can be broken by presenting self antigens and co-stimulatory molecules on FDCs. The ability to deliberately break B cell tolerance and induce self-regulated auto-Abs provide potential novel therapies targeting endogenous mediators of chronic inflammation & hypersensitivity diseases.