Cutting Edge: Distinct waves of BCL6 expression during T follicular helper cell development.

T follicular helper (T(FH)) cells are central to the development and regulation of T cell-dependent humoral immune responses. The transcriptional repressor BCL6 is required for T(FH) responses, but the kinetics of BCL6 protein expression in activated CD4(+) T cells have not been established. We measured BCL6 expression during T(FH) cell development at the single-cell level using intracellular staining and YFP-BCL6 fusion protein reporter mice. BCL6 was immediately upregulated in all dividing T cells during dendritic cell-T cell interactions. A second wave of early BCL6 expression coincided with the induction of CXCR5, resulting in a distinct and stable T(FH) cell population. Cognate B cells were not required for the induction of BCL6, but supported the expansion of T(FH) cells. These data suggest that BCL6 participates in very early events in T(FH) cell development, and that repeated encounters with APCs reinforce BCL6 expression, thereby establishing the T(FH) cell phenotype.