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Title: Defining AP4- and MYC-regulated gene expression programs in germinal center B cells during cyclic re-entry      
dateReleased:
08-23-2016
description:
B cells diversify and affinity-mature their antigen receptor repertoire in germinal centers (GC). GC B cells receive help signals during transient interaction with T cells, yet it remains unknown how these transient T-B interactions sustain the subsequent proliferative program of selected B cells. Here we show that the transcription factor AP4 is required for sustained GC B cell proliferation and subsequent establishment of a diverse and protective antibody repertoire. AP4 is induced by c-MYC during the T-B interactions and maintained by T cell-derived IL-21. B cell-specific deletion of AP4 resulted in reduced GC sizes and somatic hypermutation and a failure to control chronic viral infection. These results indicate that AP4 integrates T cell-mediated selection and sustained expansion of GC B cells for humoral immunity. Splenic B cells activated with anti-IgM and CD40L in vitro and germinal center B cells sorted from C57BL/6 mice eight days after immunization with sheep red blood cells (SRBCs) were obtained and genome-wide occupancy of c-MYC, AP4 and active histone marks was profiled by chromatin immunoprecipitation and high-throughput sequencing. Gene expression in MYC–AP4– LZ, MYC+AP4+ LZ, AP4+ DZ, and AP– DZ GC B cells from SRBC-immunized AP4-mCherry / c-MYC-GFP dual reporter mice was profiled by RNA-seq.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-80669
refinement:
raw
alternateIdentifiers:
80669
keywords:
functional genomics
dateModified:
09-12-2016
availability:
available
types:
gene expression
name:
Mus musculus
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80669/E-GEOD-80669.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80669/E-GEOD-80669.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80669
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress

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