NIAID Scientists Find B Cell Survival is a Race Against the Clock

Long-lived immune cells called memory B cells “remember” past infections by producing antibodies specific to a particular pathogen. In this way, our immune systems can mount a protective response if re-exposed to the same invader. How do they stay alive long enough to do so? New research from NIAID scientists reveals that the timing of chemical signals is key to keeping B cells from self-destructing.

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

Nature Immunology (2018) | Download Citation

Abstract

B cells are activated by two temporally distinct signals, the first provided by the binding of antigen to the B cell antigen receptor (BCR), and the second provided by helper T cells. Here we found that B cells responded to antigen by rapidly increasing their metabolic activity, including both oxidative phosphorylation and glycolysis. In the absence of a second signal, B cells progressively lost mitochondrial function and glycolytic capacity, which led to apoptosis. Mitochondrial dysfunction was a result of the gradual accumulation of intracellular calcium through calcium response–activated calcium channels that, for approximately 9 h after the binding of B cell antigens, was preventable by either helper T cells or signaling via the receptor TLR9. Thus, BCR signaling seems to activate a metabolic program that imposes a limited time frame during which B cells either receive a second signal and survive or are eliminated.