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

Bendall HH, Sikes ML, Ballard DW, Oltz EM
Mol Immunol. 1999 36 (3): 187-95

PMID: 10403484 · DOI:10.1016/s0161-5890(99)00031-0

Members of the NF-kappaB/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-kappaB subunits exhibit distinct defects in B lymphocyte activation and survival. However, the role of NF-kappaB 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-kappaB in humoral immune compartments, transgenic mice were generated that express a transdominant form of Ikappa-Balpha in B lineage cells. Whereas expression of the inhibitor had only modest effects on basal or LPS-induced levels of NF-kappaB, transgenic B cells were significantly impaired for cellular proliferation and NF-kappaB 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-kappaB levels above a stringent threshold for proper regulation of B cell homeostasis.

MeSH Terms (18)

Animals B-Lymphocyte Subsets Bone Marrow Cell Differentiation Cells, Cultured DNA-Binding Proteins I-kappa B Proteins Lymphocyte Activation Lymphocyte Depletion Mice Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic NF-kappa B NF-KappaB Inhibitor alpha Receptors, Antigen, B-Cell Signal Transduction Spleen

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