Title: | Defining AP4- and MYC-regulated gene expression programs in germinal center B cells during cyclic re-entry
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dateReleased: |
08-23-2016
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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.
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privacy: |
not applicable
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aggregation: |
instance of dataset
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ID: |
E-GEOD-80669
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refinement: |
raw
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alternateIdentifiers: |
80669
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keywords: |
functional genomics
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dateModified: |
09-12-2016
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availability: |
available
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types: |
gene expression
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name: |
Mus musculus
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80669/E-GEOD-80669.raw.1.zip![]() |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80669/E-GEOD-80669.processed.1.zip |
storedIn: |
ArrayExpress
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qualifier: |
gzip compressed
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format: |
TXT
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accessType: |
download
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authentication: |
none
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authorization: |
none
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accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80669 |
storedIn: |
Gene Expression Omnibus
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qualifier: |
not compressed
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format: |
HTML
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accessType: |
landing page
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primary: |
true
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authentication: |
none
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authorization: |
none
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abbreviation: |
EBI
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homePage: | http://www.ebi.ac.uk/ |
ID: |
SCR:004727
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name: |
European Bioinformatics Institute
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homePage: | https://www.ebi.ac.uk/arrayexpress/ |
ID: |
SCR:002964
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name: |
ArrayExpress
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