Establishing the Follicular Helper Identity George Kassiotis, Anne O'Garra  Immunity  Volume 31, Issue 3, Pages 450-452 (September 2009) DOI: 10.1016/j.immuni.2009.08.017 Copyright © 2009 Elsevier Inc. Terms and Conditions

Figure 1 Bcl-6 Drives Tfh Differentiation Tfh cells represent a subset of Th cells, distinguishable from Th1, Th2, Treg, and Th17 cell subsets. Bcl-6 expression induces the Tfh cell differentiation program in Th cell precursors. Bcl-6 overexpression can also divert Th cells at the early stages of commitment to other Th cell subsets into the Tfh cell lineage, and may even convert fully differentiated Th1, Th2, Th17, or Treg cells into Tfh cells. Bcl-6 expression is induced by IL-6 and the autocrine action of IL-21 and is suppressed by Blimp-1. In turn, Bcl-6 represses Blimp-1, expression or activity of Th1 cell regulator T-bet, Th2 cell regulator GATA3, and Th17 cell regulator RORγt. The balance of these transcription factors determines the composite helper effect of the T cell on B cells. Bcl-6 additionally represses clusters of miRNAs, which negatively regulate CXCR5, CXCR4, PD-1, and ICOS. Expression of the latter accessory molecules is thus indirectly induced. Bcl-6 also induces expression of BTLA, CD200, and the receptors for IL-6 and IL-21; however, the precise mechanism of this induction is currently unclear. Immunity 2009 31, 450-452DOI: (10.1016/j.immuni.2009.08.017) Copyright © 2009 Elsevier Inc. Terms and Conditions