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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., Herzog, S., Labi, V., Yasuda, T., Köchert, K., Janz, M., Villunger, A., 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 |
| ISSN: | 0027-8424 |
| Publisher: | National Academy of Sciences |
| Volume: | 113 |
| Number: | 18 |
| 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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