A new study from the Batista Lab at the Ragon Institute, published in the Journal of Experimental Medicine, reveals that B cells depend on a cellular cleanup process to successfully transform into the plasma cells that produce protective antibodies.

When B cells encounter a pathogen, they must rapidly shift their metabolism, which includes increasing their number of mitochondria. However, when these activated B cells differentiate into plasma cells, these excessive mitochondria must be cleared. The Batista Lab found that a protein called FIP200—known for its role in autophagy, the cell’s recycling system—is essential for this process.

In mice lacking FIP200 in their B cells, the team observed dramatically weakened immune responses, with fewer plasma cells forming after vaccination and reduced antibody production over time. Looking more closely, they found that FIP200-deficient B cells accumulated damaged mitochondria and had impaired production of heme, a molecule critical for cellular energy and metabolism.

Without the ability to clear out malfunctioning mitochondria—a process called mitophagy—B cells experienced elevated oxidative stress and struggled to activate the gene programs needed to become plasma cells.

Remarkably, when the researchers added heme directly to FIP200-deficient B cells in culture, plasma cell differentiation was restored. This suggests that the metabolic defects caused by mitochondrial dysfunction can be bypassed by supplying the missing building blocks.

The findings illuminate how the immune system’s antibody response depends on precise metabolic regulation and point to heme metabolism as a potential target for enhancing immune responses in settings where antibody production is impaired.