Bibliographic Details
| Title: |
Canonical NF-κB signaling is uniquely required for the long-term persistence of functional mature B cells. |
| Authors: |
Derudder, Emmanuel, Herzog, Sebastian, Labi, Verena, Tomoharu Yasuda, Köchert, Karl, Janz, Martin, Villunger, Andreas, Schmidt-Supprian, Marc, Rajewsky, Klaus |
| Source: |
Proceedings of the National Academy of Sciences of the United States of America; 5/3/2016, Vol. 113 Issue 18, p5065-5070, 6p |
| Subject Terms: |
B cells, NF-kappa B, CELL differentiation, KINASES, TRANSCRIPTION factors |
| 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. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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