Paul W. Bible Kristina T. Lu Yuka Kanno Jennifer L. Cannons Robin Handon et al.
10-01-2011
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-..
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) cells. SAP-deficient Tfh-like cells appeared virtually indistinguishable from wild-type, 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 cell characteristics. ChIP-Seq analyses revealed positive epigenetic markings on Tbx21, Gata3, and Rorc in Tfh-like and ex vivo Tfh cells and on Bcl6 in non-Tfh cells, supporting the concept of plasticity between Tfh and other Th cell populations.
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Lu KT, Kanno Y, Cannons JL, Handon R, Bible PW, Elkahloun AG, Anderson SM, Wei L, Sun HW, O'Shea JJ, Schwartzberg PL. Functional and epigenetic studies reveal multistep differentiation and plasticity..
Lu KT, Kanno Y, Cannons JL, Handon R, Bible PW, Elkahloun AG, Anderson SM, Wei L, Sun HW, O'Shea JJ, Schwartzberg PL. Functional and epigenetic studies reveal multistep differentiation and plasticity of in vitro-generated and in vivo-derived follicular T helper cells. Immunity. 2011. doi: 10.1016/j.immuni.2011.07.015