IgE induction by parasites and allergens is antigen driven and cognate T cell help dependent. We demonstrate that spontaneously produced IgE in T cell-deficient and germ-free wild-type (wt) mice is composed of natural specificities and induced by a mechanism independent of MHC class II (MHC II) cognate help. This does not require secondary lymphoid structures or germinal center formation, although some bystander T cell-derived IL-4 is necessary. The pathway of spontaneous IgE production is not inhibited by regulatory T cells and increases with age to constitute significant serum concentrations, even in naive animals.