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Accession IconGSE32624

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

Organism Icon Mus musculus
Sample Icon 6 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

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Description
Follicular T helper cells (Tfh) are critical for providing help to B cells for germinal center (GC) formation. Mutations affecting 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 IL-21, Tfh markers, and Bcl6, and rescued GC formation in SAP-deficient hosts substantially 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, other Th cell populations 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 cells, supporting the concept of plasticity between Tfh and other Th populations.
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