Second signals rescue B cells from activation-induced mitochondrial dysfunction and death

B cells are activated by two temporally distinct signals, the first provided by antigen binding to the B cell antigen receptor (BCR) and the second by T helper cells. Here we show that B cells responded to antigen by rapidly increasing metabolic activity including both oxidative phosphorylation and glycolysis. In the absence of a second signal B cells progressively lost mitochondrial function and glycolytic capacity leading to apoptosis. Mitochondrial dysfunction was a result of the gradual accumulation of intracellular calcium through calcium response activated calcium channels that was preventable for approximately nine hours after B cell antigen binding by either T helper cells or Toll-like receptor 9 signaling. Thus, BCR signaling appears to activate a metabolic program that imposes a limited time window in which B cells either receive a second signal and survive or are eliminated.