The transcription factor TCF-1 initiates the differentiation of TFH cells during acute viral infection

Induction of the transcriptional repressor BcI-6 in CD4(+) T cells is critical for the differentiation of follicular helper T cells (T-FH cells), which are essential for B cell mediated immunity. In contrast, the transcription factor Blimp1 (encoded by Prdm1) inhibits T-FH differentiation by antagonizing BcI-6. Here we found that the transcription factor TCF-1 was essential for both the initiation of TFH differentiation and the effector function of differentiated T-FH cells during acute viral infection. Mechanistically, TCF-1 bound directly to the Bcl6 promoter and Prdm1 5' regulatory regions, which promoted BcI-6 expression but repressed Blimp1 expression. ICE-1-null T-FH cells upregulated genes associated with non-T-FH cell lineages. Thus, TCF-1 functions as an important hub upstream of the Bcl-6-Blimp1 axis to initiate and secure the differentiation of T-FH cells during acute viral infection.