Figure 2.

Common linear differentiation, lineage divergence, and progressive restriction. (A) Upon activation, naive cells establish a common linear differentiation program that installs multiple capacities in postactivation cells, such as responsiveness to multiple chemokines, cytokines, and additional costimulatory and coinhibitory receptors, engages migratory capabilities, metabolic capacities, effector functions, and, importantly, comingles expression of regulatory factors that are normally associated with one or another dedicated cell fate. This initial process would facilitate cells to ultimately adopt one of many potential differentiated outcomes later, while being committed to none of them initially, rather serving as progenitors of both terminally differentiated and memory cell progenies. (B) Stochastic transcriptional events result in metastable gene and protein expression states that causes transient lineage bias in some cells among an otherwise homogeneous population (Chang et al. 2008). (C) Cell fate–determining factors reinforce these spontaneous fluctuations, encouraging differentiation along one pathway by enhancing gene expression of the chosen direction, while silencing gene expression that opposes the alternative path at the chromatin level. Cells may interconvert (arrows) until late in their paths.