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A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells
BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular ne...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889572/ https://www.ncbi.nlm.nih.gov/pubmed/25497099 http://dx.doi.org/10.1016/j.celrep.2014.11.024 |
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author | Almaden, Jonathan V. Tsui, Rachel Liu, Yi C. Birnbaum, Harry Shokhirev, Maxim N. Ngo, Kim A. Davis-Turak, Jeremy C. Otero, Dennis Basak, Soumen Rickert, Robert C. Hoffmann, Alexander |
author_facet | Almaden, Jonathan V. Tsui, Rachel Liu, Yi C. Birnbaum, Harry Shokhirev, Maxim N. Ngo, Kim A. Davis-Turak, Jeremy C. Otero, Dennis Basak, Soumen Rickert, Robert C. Hoffmann, Alexander |
author_sort | Almaden, Jonathan V. |
collection | PubMed |
description | BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences. |
format | Online Article Text |
id | pubmed-4889572 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
record_format | MEDLINE/PubMed |
spelling | pubmed-48895722016-06-02 A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells Almaden, Jonathan V. Tsui, Rachel Liu, Yi C. Birnbaum, Harry Shokhirev, Maxim N. Ngo, Kim A. Davis-Turak, Jeremy C. Otero, Dennis Basak, Soumen Rickert, Robert C. Hoffmann, Alexander Cell Rep Article BAFF, an activator of the noncanonical NFκB pathway, provides critical survival signals during B cell maturation and contributes to B cell proliferation. We found that the NFκB family member RelB is required ex vivo for B cell maturation, but cRel is required for proliferation. Combined molecular network modeling and experimentation revealed Nfkb2 p100 as a pathway switch; at moderate p100 synthesis rates in maturing B cells, BAFF fully utilizes p100 to generate the RelB:p52 dimer, whereas at high synthesis rates, p100 assembles into multimeric IκBsome complexes, which BAFF neutralizes in order to potentiate cRel activity and B cell expansion. Indeed, moderation of p100 expression or disruption of IκBsome assembly circumvented the BAFF requirement for full B cell expansion. Our studies emphasize the importance of p100 in determining distinct NFκB network states during B cell biology, which causes BAFF to have context-dependent functional consequences. 2014-12-11 2014-12-24 /pmc/articles/PMC4889572/ /pubmed/25497099 http://dx.doi.org/10.1016/j.celrep.2014.11.024 Text en This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/). |
spellingShingle | Article Almaden, Jonathan V. Tsui, Rachel Liu, Yi C. Birnbaum, Harry Shokhirev, Maxim N. Ngo, Kim A. Davis-Turak, Jeremy C. Otero, Dennis Basak, Soumen Rickert, Robert C. Hoffmann, Alexander A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells |
title | A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells |
title_full | A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells |
title_fullStr | A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells |
title_full_unstemmed | A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells |
title_short | A Pathway Switch Directs BAFF Signaling to Distinct NFκB Transcription Factors in Maturing and Proliferating B Cells |
title_sort | pathway switch directs baff signaling to distinct nfκb transcription factors in maturing and proliferating b cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4889572/ https://www.ncbi.nlm.nih.gov/pubmed/25497099 http://dx.doi.org/10.1016/j.celrep.2014.11.024 |
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