Analysis of bistability in the gene regulatory network underlying B cell terminal differentiation (see Additional File 1: Supplementary Material for model details). (A) Steady-state stimulus-response curves between Blimp-1 and Pax5 under zero LPS and TCDD. The red curve was obtained with Blimp-1 level as the independent variable (i.e., stimulus) and the steady-state level of Pax5 as the response; the blue curve was obtained with Pax5 level as the independent variable and the steady-state level of Blimp-1 as the response. The blue curve represents an ultrasensitive response of Blimp-1 to Pax5 due to the presence of the Bcl-6/Blimp-1 double-negative feedback loop. The ultrasensitivity enables the blue curve to intersect with the red curve at three points, indicative of bistability. Intersection point 1 represents the stable B cell state; intersection point 3 represents the stable plasma cell state; and intersection point 2 is an unstable steady state. (B) Bifurcation analysis using AP-1p (active form of AP-1) as the independent parameter. Vertical arrows indicate that there is a deterministic threshold value of AP-1p required to turn on the bistable switch. Leftward arrows indicate that the bistable switch is irreversible even when AP-1p drops back to the basal level of 100.