Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2016-05, Vol.113 (18), p.5065-5070

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.