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

Members of the NF-kappa B/Rel transcription factor family are expressed con stitutively during B cell development and are further induced by mitogen ac tivation. Mice harboring germline disruptions in individual NF-kappa B subu nits exhibit distinct defects in B lymphocyte activation and survival. Howe ver, the role of NF-kappa B in the production and maintenance of B cell sub sets has been difficult to dissect in these knockout animals due to functio nal impairment of other immune cells. To directly address the cell autonomo us requirements for NF-kappa B in humoral immune compartments, transgenic m ice 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 effec ts on basal or LPS-induced levels of NF-kappa B, transgenic B cells were si gnificantly impaired for cellular proliferation and NF-kappa B induction in response to B cell receptor (BCR) crosslinking. Furthermore, the trans-dom inant inhibitor produced a dose-dependent reduction in the population of ma ture splenic B cells. This cellular defect was more pronounced in long-live d 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 homeos tasis. (C) 1999 Elsevier Science Ltd. All rights reserved.