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http://hdl.handle.net/123456789/585
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DC Field | Value | Language |
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dc.contributor.author | Hoffmann, Alexander | - |
dc.date.accessioned | 2015-06-10T09:49:05Z | - |
dc.date.available | 2015-06-10T09:49:05Z | - |
dc.date.issued | 2014-12 | - |
dc.identifier.uri | http://hdl.handle.net/123456789/585 | - |
dc.description.abstract | 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. | en_US |
dc.publisher | Elsevier Inc. | en_US |
dc.title | A pathway switch directs BAFF signaling to distinct NFκB transcription factors in maturing and proliferating B cells | en_US |
dc.contributor.coauthor | Almaden, Jonathan V | - |
dc.contributor.coauthor | Tsui, Rachel | - |
dc.contributor.coauthor | Liu, Yi C | - |
dc.contributor.coauthor | Birnbaum, Harry | - |
dc.contributor.coauthor | Shokhirev, Maxim N | - |
dc.contributor.coauthor | Ngo, Kim A | - |
dc.contributor.coauthor | Davis-Turak, Jeremy C | - |
dc.contributor.coauthor | Otero, Dennis | - |
dc.contributor.coauthor | Basak, Soumen | - |
dc.contributor.coauthor | Rickert, Robert C | - |
dc.journal | Cell Reports | en_US |
dc.volumeno | 9 | en_US |
dc.issueno | 6 | en_US |
dc.pages | 2098-2111 | en_US |
Appears in Collections: | Systems Immunology, Publications |
Files in This Item:
File | Description | Size | Format | |
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2014_Almaden et. al.pdf | 4.15 MB | Adobe PDF | View/Open Request a copy |
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