Mitogen-independent cell cycle progression in B lymphocytes

Abstract

The canonical view of the cell cycle posits that G1 progression signals are essential after each mitosis to enter S phase. A subset of tumor cells bypass this requirement and progress to the next cell division in the absence of continued signaling. B and T lymphocytes of the adaptive immune system undergo a proliferative burst, termed clonal expansion, to generate pools of antigen specific cells for effective immunity. There is evidence that rules for lymphocyte cell division digress from the canonical model. Here we show that B lymphocytes sustain several rounds of mitogen-independent cell division following the first mitosis. Such division is driven by unique characteristics of the post mitotic G1 phase and limited by extensive cell death that can be circumvented by appropriate anti-apoptotic signals. An essential component for continued cell division is Birc5 (survivin), a protein associated with chromosome segregation in G2/M. Our observation provides direct evidence for Pardees hypothesis that retention of features of G2M in post-mitotic cells could trigger further cell cycle progression. The partially active G1 phase and propensity for apoptosis that is inherited after each division may permit rapid burst of proliferation and cell death that are hallmarks of immune responses.