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231224s2016 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2016.10.018
|2 doi
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|a pubmed24n0886.xml
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|a (DE-627)NLM265954576
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|a (NLM)27816669
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Dam, Elizabeth M
|e verfasserin
|4 aut
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|a The BANK1 SLE-risk variants are associated with alterations in peripheral B cell signaling and development in humans
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|c 2016
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 31.05.2017
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|a Date Revised 13.11.2018
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2016 Elsevier Inc. All rights reserved.
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|a Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the development of autoantibodies that drive disease pathogenesis. Genetic studies have associated nonsynonymous variants in the BANK1 B cell scaffolding gene with susceptibility to SLE and autoantibodies in lupus. To determine how the BANK1 SLE-risk variants contribute to the dysregulated B cell program in lupus, we performed genotype/phenotype studies in human B cells. Targeted phospho-proteomics were used to evaluate BCR/CD40 signaling in human B cell lines engineered to express the BANK1 risk or non-risk variant proteins. We found that phosphorylation of proximal BCR signaling molecules was reduced in B cells expressing the BANK1 risk protein compared to the non-risk protein. Similar to these findings, we observed decreased B cell signaling in primary B cells from genotyped healthy control subjects carrying the BANK1 risk haplotype, including blunted BCR- and CD40-dependent AKT activation. Consistent with decreased AKT activation, we found that BANK1 risk B cells expressed increased basal levels of FOXO1 protein and increased expression of FOXO1 target genes upon stimulation compared to non-risk B cells. Healthy subjects carrying the BANK1 risk haplotype were also characterized by an expansion of memory B cells. Taken together, our results suggest that the SLE susceptibility variants in the BANK1 gene may contribute to lupus by altering B cell signaling, increasing FOXO1 levels, and enhancing memory B cell development
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|a Journal Article
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|a Adaptor Proteins, Signal Transducing
|2 NLM
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| 650 |
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|a BANK1 protein, human
|2 NLM
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| 650 |
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|a FOXO1 protein, human
|2 NLM
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| 650 |
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|a Forkhead Box Protein O1
|2 NLM
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| 650 |
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|a Membrane Proteins
|2 NLM
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| 700 |
1 |
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|a Habib, Tania
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Chen, Janice
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Funk, Andrew
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Glukhova, Veronika
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Davis-Pickett, Mel
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wei, Shan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a James, Richard
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Buckner, Jane H
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cerosaletti, Karen
|e verfasserin
|4 aut
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| 773 |
0 |
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|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 173(2016) vom: 01. Dez., Seite 171-180
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
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|g volume:173
|g year:2016
|g day:01
|g month:12
|g pages:171-180
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|u http://dx.doi.org/10.1016/j.clim.2016.10.018
|3 Volltext
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