Bcl6 and Blimp-1 Are Reciprocal and Antagonistic Regulators of T Follicular Helper Cell Differentiation

T Follicular Helper Cell Differentiation

When B cells respond to an infection, they often require help from CD4 ⁺ T cells to mount a proper response. It is thought that a subset of CD4 ⁺ effector T cells, called T follicular helper cells (T _FH ), performs this function. Several subsets of effector CD4 ⁺ T cells arise, depending on the type of infection, which have distinct transcriptional programs driving their differentiation. Whether this is also the case for T _FH cells has not been clear (see the Perspective by Awasthi and Kuchroo ). Nurieva et al. (p. 1001 , published online 23 July) and Johnston et al. (p. 1006 ; published online 16 July) now demonstrate that the transcription factor Bcl6 is both necessary and sufficient for T _FH differentiation and subsequent B cell–mediated immunity, suggesting that it is a master regulator of this lineage. Johnston et al. also show that expression of Bcl6 and the transcription factor, Blimp-1, are reciprocally regulated in T _FH cells and that, when ectopically expressed, Blimp-1 inhibits T _FH development.