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Canonical NF-κB signaling is uniquely required for the long-term persistence of functional mature B cells

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Item Type:Article
Title:Canonical NF-κB signaling is uniquely required for the long-term persistence of functional mature B cells
Creators Name:Derudder, E. and Herzog, S. and Labi, V. and Yasuda, T. and Köchert, K. and Janz, M. and Villunger, A. and Schmidt-Supprian, M. and Rajewsky, K.
Abstract:Although canonical NF-κB signaling is crucial to generate a normal mature B-cell compartment, its role in the persistence of resting mature B cells is controversial. To resolve this conflict, we ablated NF-κB essential modulator (NEMO) and I{kappa}B kinase 2 (IKK2), two essential mediators of the canonical pathway, either early on in B-cell development or specifically in mature B cells. Early ablation severely inhibited the generation of all mature B-cell subsets, but follicular B-cell numbers could be largely rescued by ectopic expression of B-cell lymphoma 2 (Bcl2), despite a persisting block at the transitional stage. Marginal zone (MZ) B and B1 cells were not rescued, indicating a possible role of canonical NF-κB signals beyond the control of cell survival in these subsets. When canonical NF-κB signaling was ablated specifically in mature B cells, the differentiation and/or persistence of MZ B cells was still abrogated, but follicular B-cell numbers were only mildly affected. However, the mutant cells exhibited increased turnover as well as functional deficiencies upon activation, suggesting that canonical NF-κB signals contribute to their long-term persistence and functional fitness.
Keywords:NF-{kappa}B, Canonical Signaling, Follicular B Cells, Persistence, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:5065-5070
Date:3 May 2016
Official Publication:https://doi.org/10.1073/pnas.1604529113
PubMed:View item in PubMed

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