Bcl6 is required for the development of T follicular helper cells marked by downregulation of P-selectin glycoprotein ligand-1

Follicular helper T cells (TFH), defined by expression of the surface markers CXCR5, PD-1 and ICOS, are located in germinal centers where they provide help for B cell maturation through the secretion of IL-21. The transcriptional repressor Bcl6 is upregulated in TFH cells; however, the role that it plays in their development is unknown. We describe downregulation of P-selectin glycoprotein ligand-1 (PSGL1) as a new surface marker for TFH cells, and show that Bcl6 is required for the development of TFH cells that are PSGL1lo. Activated antigen-specific CD4 PSGL1lo T cells are enriched for expression of CXCR5 and PD-1, and highly upregulate IL-21 and Bcl6. Over-expression of Bcl6 leads to an increase in PSGL1lo TFH cells; however, it cannot rescue TFH cell development in the absence of ICOS. Consistent with others, we find B cells are required for full development of TFH cells, but not for downregulation of PSGL1, suggesting there are multiple steps in development of the subset. This data demonstrates that Bcl6, independent of ICOS signaling, is critical for the development of this lineage.