In the 40 years since Harvard medical student Gilbert Omenn first described a rare, inherited disorder producing a paradoxical combination of immunodeficiency and immune dysregulation, the pathogenesis of Omenn syndrome (OS) has remained mysterious. In separate studies reported in this issue of the JCI, two mouse models bearing mutations in the V(D)J recombinase analogous to those causing human OS have been shown to recapitulate the disease and provide insight into the genesis of immunodeficiency combined with autoimmunity and atopy in OS and other disease settings (see the related articles beginning on pages 1260 and 1270).
