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

Emmanuel Derudder, Sebastian Herzog, Verena Labi, Tomoharu Yasuda, Karl Köchert, Martin Janz, Andreas Villunger, Marc Schmidt-Supprian, Klaus Rajewsky

Research output: Contribution to journalArticlepeer-review

12 Citations (Scopus)

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 IκB 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.

Original languageEnglish
Pages (from-to)5065-5070
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number18
DOIs
Publication statusPublished - May 3 2016

All Science Journal Classification (ASJC) codes

  • General

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