Production of autoantibodies and IgE antibodies by B lymphocytes must be tightly controlled to avoid rampant autoimmune or allergic disease. Mutation of the gene encoding the pro-apoptotic receptor FAS causes Autoimmune Lymphoproliferative Syndrome (ALPS), where production of autoantibodies is thought to occur through failure of FAS-mediated removal of self-reactive germinal centre (GC) B cells. We have found that FAS is in fact not required for this process. Instead, FAS-deficiency leads to the emergence of "rogue" GC B cells that escape normal antigen selection, continue somatic hypermutation and differentiate into large populations of clonally restricted, antibody-secreting plasma cells. This includes 100-fold increased numbers of IgE-producing plasma cells, leading us to identify a major cohort of ALPS patients displaying hyper-IgE. We propose that the release of uncontrolled, rogue GC B cells brought about by mutation of FAS or related regulatory lesions represents a major driver of antibody-mediated immunopathologies in humans and mice.