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Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits
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| Zeitschriftentitel: | Journal of Experimental Medicine |
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| Personen und Körperschaften: | , , , , , , |
| In: | Journal of Experimental Medicine, 211, 2014, 10, S. 2103-2118 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Rockefeller University Press
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>Germinal centers (GCs) are the sites where memory B cells and plasma cells producing high-affinity antibodies are generated during T cell–dependent immune responses. The molecular control of GC B cell maintenance and differentiation remains incompletely understood. Activation of the NF-κB signaling pathway has been implicated; however, the distinct roles of the individual NF-κB transcription factor subunits are unknown. We report that GC B cell–specific deletion of the NF-κB subunits c-REL or RELA, which are both activated by the canonical NF-κB pathway, abolished the generation of high-affinity B cells via different mechanisms acting at distinct stages during the GC reaction. c-REL deficiency led to the collapse of established GCs immediately after the formation of dark and light zones at day 7 of the GC reaction and was associated with the failure to activate a metabolic program that promotes cell growth. Conversely, RELA was dispensable for GC maintenance but essential for the development of GC-derived plasma cells due to impaired up-regulation of BLIMP1. These results indicate that activation of the canonical NF-κB pathway in GC B cells controls GC maintenance and differentiation through distinct transcription factor subunits. Our findings have implications for the role of NF-κB in GC lymphomagenesis.</jats:p> |
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| Umfang: | 2103-2118 |
| ISSN: |
1540-9538
0022-1007 |
| DOI: | 10.1084/jem.20132613 |