Even after two and a half decades since its discovery, the basic mechanism behind the cytoplasmic localization of inactive NF-κB complexes remains incompletely understood. Based on our cell-based studies, we developed a new animal model to study the regulation of subcellular localization of NF-κB complexes. This animal model has led us to learn more about development, maturation and function of B lymphocytes, cells that make antibodies in our bodies. It also led to the investigation of the development of secondary lymphoid organs and tissues. These studies are revealing the presence of multiple mechanisms that control subcellular distribution of NF-κB proteins. Dysregulation of such localization causes surprisingly widespread developmental defects. We are creating additional mouse models to further test this fundamental aspect of the NF-κB signaling system.