An intact NF-κB signaling pathway is required for maintenance of mature B cell subsets

Members of the NF-kappa B/Rel transcription factor family are expressed constitutively during B cell development and are further induced by mitogen activation. Mice harboring germline disruptions in individual NF-kappa B subunits exhibit distinct defects in B lymphocyte activation and survival. However, the role of NF-kappa B in the production and maintenance of B cell subsets has been difficult to dissect in these knockout animals due to functional impairment of other immune cells. To directly address the cell autonomous requirements for NF-kappa B in humoral immune compartments, transgenic mice were generated that express a trans-dominant form of I kappa B alpha in B lineage cells. Whereas expression of the inhibitor had only modest effects on basal or LPS-induced levels of NF-kappa B, transgenic B cells were significantly impaired for cellular proliferation and NF-kappa B induction in response to B cell receptor (BCR) crosslinking. Furthermore, the trans-dominant inhibitor produced a dose-dependent reduction in the population of mature splenic B cells. This cellular defect was more pronounced in long-lived B lymphocyte subsets that recirculate to the adult bone marrow. Together, these results indicate that BCR-mediated signaling must maintain NF-kappa B levels above a stringent threshold for proper regulation of B cell homeostasis. (C) 1999 Elsevier Science Ltd. All rights reserved.