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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 |
|---|---|
| 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: |
| author_facet |
Heise, Nicole De Silva, Nilushi S. Silva, Kathryn Carette, Amanda Simonetti, Giorgia Pasparakis, Manolis Klein, Ulf Heise, Nicole De Silva, Nilushi S. Silva, Kathryn Carette, Amanda Simonetti, Giorgia Pasparakis, Manolis Klein, Ulf |
|---|---|
| author |
Heise, Nicole De Silva, Nilushi S. Silva, Kathryn Carette, Amanda Simonetti, Giorgia Pasparakis, Manolis Klein, Ulf |
| spellingShingle |
Heise, Nicole De Silva, Nilushi S. Silva, Kathryn Carette, Amanda Simonetti, Giorgia Pasparakis, Manolis Klein, Ulf Journal of Experimental Medicine Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits Immunology Immunology and Allergy |
| author_sort |
heise, nicole |
| spelling |
Heise, Nicole De Silva, Nilushi S. Silva, Kathryn Carette, Amanda Simonetti, Giorgia Pasparakis, Manolis Klein, Ulf 1540-9538 0022-1007 Rockefeller University Press Immunology Immunology and Allergy http://dx.doi.org/10.1084/jem.20132613 <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> Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits Journal of Experimental Medicine |
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| title |
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_unstemmed |
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_full |
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_fullStr |
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_full_unstemmed |
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_short |
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_sort |
germinal center b cell maintenance and differentiation are controlled by distinct nf-κb transcription factor subunits |
| topic |
Immunology Immunology and Allergy |
| url |
http://dx.doi.org/10.1084/jem.20132613 |
| publishDate |
2014 |
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2103-2118 |
| description |
<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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| author | Heise, Nicole, De Silva, Nilushi S., Silva, Kathryn, Carette, Amanda, Simonetti, Giorgia, Pasparakis, Manolis, Klein, Ulf |
| author_facet | Heise, Nicole, De Silva, Nilushi S., Silva, Kathryn, Carette, Amanda, Simonetti, Giorgia, Pasparakis, Manolis, Klein, Ulf, Heise, Nicole, De Silva, Nilushi S., Silva, Kathryn, Carette, Amanda, Simonetti, Giorgia, Pasparakis, Manolis, Klein, Ulf |
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| description | <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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| institution | DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1 |
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| spelling | Heise, Nicole De Silva, Nilushi S. Silva, Kathryn Carette, Amanda Simonetti, Giorgia Pasparakis, Manolis Klein, Ulf 1540-9538 0022-1007 Rockefeller University Press Immunology Immunology and Allergy http://dx.doi.org/10.1084/jem.20132613 <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> Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits Journal of Experimental Medicine |
| spellingShingle | Heise, Nicole, De Silva, Nilushi S., Silva, Kathryn, Carette, Amanda, Simonetti, Giorgia, Pasparakis, Manolis, Klein, Ulf, Journal of Experimental Medicine, Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits, Immunology, Immunology and Allergy |
| title | Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_full | Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_fullStr | Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_full_unstemmed | Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_short | Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| title_sort | germinal center b cell maintenance and differentiation are controlled by distinct nf-κb transcription factor subunits |
| title_unstemmed | Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits |
| topic | Immunology, Immunology and Allergy |
| url | http://dx.doi.org/10.1084/jem.20132613 |