| First Author | Heise N | Year | 2014 |
| Journal | J Exp Med | Volume | 211 |
| Issue | 10 | Pages | 2103-18 |
| PubMed ID | 25180063 | Mgi Jnum | J:228566 |
| Mgi Id | MGI:5707770 | Doi | 10.1084/jem.20132613 |
| Citation | Heise N, et al. (2014) Germinal center B cell maintenance and differentiation are controlled by distinct NF-kappaB transcription factor subunits. J Exp Med 211(10):2103-18 |
| abstractText | 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-kappaB signaling pathway has been implicated; however, the distinct roles of the individual NF-kappaB transcription factor subunits are unknown. We report that GC B cell-specific deletion of the NF-kappaB subunits c-REL or RELA, which are both activated by the canonical NF-kappaB 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-kappaB pathway in GC B cells controls GC maintenance and differentiation through distinct transcription factor subunits. Our findings have implications for the role of NF-kappaB in GC lymphomagenesis. |
