Fig. 3.

Irreversibility due to cosignaling of BCR and CD40. A and B show the stationary points of a B-cell at different levels of BCR stimulation. Blue and red dotted lines indicate stable and unstable stationary points respectively. C and D show the signaling intensity through the BCR (C) and the BCR and CD40 (D) pathways as a function of time. (A) After BCR signaling, BCL6 protein is degraded (arrows a–d) but after the cessation of the signal, returns to levels prior to stimulation. (B) Coordinated BCR and CD40 stimulation promotes a jump to a different branch of stationary points leading to an irreversible plasma cell phenotype.