| First Author | Derudder E | Year | 2016 |
| Journal | Proc Natl Acad Sci U S A | Volume | 113 |
| Issue | 18 | Pages | 5065-70 |
| PubMed ID | 27099294 | Mgi Jnum | J:232206 |
| Mgi Id | MGI:5776315 | Doi | 10.1073/pnas.1604529113 |
| Citation | Derudder E, et al. (2016) Canonical NF-kappaB signaling is uniquely required for the long-term persistence of functional mature B cells. Proc Natl Acad Sci U S A 113(18):5065-70 |
| abstractText | Although canonical NF-kappaB 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-kappaB essential modulator (NEMO) and IkappaB 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-kappaB signals beyond the control of cell survival in these subsets. When canonical NF-kappaB 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-kappaB signals contribute to their long-term persistence and functional fitness. |
