Genomics

Dataset Information

304

Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro and in vivo follicular T helper cells


ABSTRACT: Follicular T helper cells (Tfh) provide critical help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated Protein (SAP) prevent GC formation due to defective T-B cell interactions, yet effects on Tfh cell differentiation remain unclear. We describe the in vitro differentiation of functionally-competent “Tfh-like” cells that expressed Interleukin-21, Tfh markers, and Bcl6, and rescued GC formation in SAP-deficient hosts better than other T helper (Th) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wildtype, yet failed to support GCs in vivo. Interestingly, both Tfh-like and in vivo-derived Tfh cells could produce effector cytokines in response to polarizing conditions. Moreover, Th1, Th2 and Th17 cells could be reprogrammed to obtain Tfh characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3 and Rorc in Tfh-like and ex vivo Tfh cells, and Bcl6 in other Th cell populations, supporting the concept of plasticity between Tfh and other Th cells. Epigenetic modifications were evaluated in ChIP-Seq studies by profiling histone H3K4 and H3K27 trimethylation marks between Th1, Th2, Th17, Tfh-like, and CXCR5+PD-1+ sorted Tfh-like in vitro generated T helper cell populations and ex vivo derived Tfh cells.

ORGANISM(S): Mus musculus  

SUBMITTER: John J O'Shea   Hongwei Sun  Pamela L Schwartzberg  Kristina T Lu  Yuka Kanno 

PROVIDER: E-GEOD-32864 | ArrayExpress | 2012-01-05

SECONDARY ACCESSION(S): GSE32864SRP008800PRJNA146549

REPOSITORIES: GEO, ArrayExpress, ENA

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Publications

Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells.

Lu Kristina T KT   Kanno Yuka Y   Cannons Jennifer L JL   Handon Robin R   Bible Paul P   Elkahloun Abdel G AG   Anderson Stacie M SM   Wei Lai L   Sun Hongwei H   O'Shea John J JJ   Schwartzberg Pamela L PL  

Immunity 20111020 4


Follicular T helper (Tfh) cells provide critical help to B cells for germinal center (GC) formation. Mutations affecting SLAM-associated protein (SAP) prevent GC formation because of defective T cell-B cell interactions, yet effects on Tfh cell differentiation remain unclear. We describe the in vitro differentiation of functionally competent "Tfh-like" cells that expressed interleukin-21, Tfh cell markers, and Bcl6 and rescued GC formation in SAP-deficient hosts better than other T helper (Th) c  ...[more]

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