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Here, focusing on survival, we compared changes in the transcriptome of pleiotropically competent, early passage L3055 Burkitt\u2019s lymphoma cells confronted with low (picomolar) and high (nanomolar) concentrations of CD154 to gain insight into how a single receptor sets these distinct phenotypes. Of 267 genes altering transcriptional activity in response to strong CD154 tone, only 25 changed coordinately on low receptor occupancy. Seven of the top nine common up-regulated genes were targets of NF-\u03baB. Direct measurement and functional inhibition of the NF-\u03baB pathway revealed it to be central to a CD40-dependent survival signature. Although the canonical NF-\u03baB axis was engaged by both signaling strengths equally, robust alternative pathway activation was a feature selective to a strong CD40 signal. Discriminatory exploitation of the two separate arms of NF-\u03baB activation may indicate a principle whereby a cell senses and reacts differentially to shifting ligand availability. Identifying components selectively coupling CD40 to each axis could indicate targets for disruption in B cell pathologies underpinned by ectopic and\/or hyper-CD154 activity such as neoplasia and some autoimmunities.<\/jats:p>","DOI":"10.4049\/jimmunol.179.5.2705","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:17:46Z","timestamp":1397848666000},"page":"2705-2712","source":"Crossref","is-referenced-by-count":17,"title":["CD154 Tone Sets the Signaling Pathways and Transcriptome Generated in Model CD40-Pluricompetent L3055 Burkitt\u2019s Lymphoma Cells"],"prefix":"10.1093","volume":"179","author":[{"given":"Ross","family":"Stewart","sequence":"first","affiliation":[{"name":"MRC Centre for Immune Regulation, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbin","family":"Wei","sequence":"additional","affiliation":[{"name":"Cancer Research United Kingdom, Institute for Cancer Studies, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Challa","sequence":"additional","affiliation":[{"name":"MRC Centre for Immune Regulation, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard J","family":"Armitage","sequence":"additional","affiliation":[{"name":"Inflammation Research , Amgen, Seattle, WA 98101"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John R","family":"Arrand","sequence":"additional","affiliation":[{"name":"Cancer Research United Kingdom, Institute for Cancer Studies, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Rowe","sequence":"additional","affiliation":[{"name":"Cancer Research United Kingdom, Institute for Cancer Studies, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lawrence S","family":"Young","sequence":"additional","affiliation":[{"name":"Cancer Research United Kingdom, Institute for Cancer Studies, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aristides","family":"Eliopoulos","sequence":"additional","affiliation":[{"name":"Cancer Research United Kingdom, Institute for Cancer Studies, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Gordon","sequence":"additional","affiliation":[{"name":"MRC Centre for Immune Regulation, University of Birmingham Medical School , Birmingham ,","place":["United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2007,9,1]]},"reference":[{"key":"2026012809234926300_R1","first-page":"269","volume-title":"Immunology","year":"2000"},{"key":"2026012809234926300_R2","first-page":"3411","volume-title":"Blood","year":"2002"},{"key":"2026012809234926300_R3","first-page":"383","volume-title":"Nature","year":"2001"},{"key":"2026012809234926300_R4","first-page":"37","volume-title":"Immunity","year":"2002"},{"key":"2026012809234926300_R5","first-page":"10717","volume-title":"Proc. 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