The early events that determine T follicular helper cell commitment in vivo are described in an elegant study from Joe Craft and colleagues. They confirmed that P-selectin glycoprotein ligand 1 (PSGL-1) is down-regulated in a population that are CXCR5high PD-1high, express BCL6 and IL-21 mRNA, and thus are TFh cells. The novelty is that they show this in response to alum-precipitated protein immunization, while they had previously observed these cells in a model of lupus-prone MRL/Faslpr mice. Interestingly, PSGL-1 down-regulation is dependent upon BCL-6 expression and precedes the up-regulation of CXCR5 and PD-1. This suggests that the modulation of PSGL-1 expression is part of the TFh cell program of differentiation. In addition, B cells were neither required for initial upregulation of BCL-6 nor PSGL-1 down-regulation, suggesting these events preceded T–B cell interactions, although they were required for full development of the TFh cell phenotype, including CXCR5 and PD-1 upregulation, and IL-21 synthesis. Finally, BCL-6 upregulation and TFh cell differentiation were independent of IL-6 and IL-21, revealing that either cytokine is not absolutely required for development of BCL-6+ TFh cells in vivo.
Shared similarities between follicular B helper T cells and extra-follicular B helper T cells?