B cells reprogram their metabolism upon activation

B cells are the immune cells that produce antibodies. At rest they are largely inactive and consume little energy. Once an activation signal arrives, they must divide rapidly and manufacture large quantities of protein. That demands an entirely different metabolic setup.

Researchers used quantitative protein analysis (proteomics) to measure which proteins increase in mouse B cells after activation through a bacterial signaling molecule (lipopolysaccharide, LPS). The result was surprisingly comprehensive. Not only did energy-generating proteins increase; the cells also strongly ramped up amino acid uptake and cholesterol production.

Amino acids and cholesterol as building blocks

Those two processes are connected. Cholesterol is needed to build cell membranes during division. Amino acids are the building blocks of the antibodies themselves. The study shows that B cells produce specific transporter proteins to pull in amino acids faster. At the same time, they activate a range of enzymes for internal cholesterol synthesis, rather than importing it from outside the cell.

This sets B cells apart from some other immune cells that, upon activation, become heavily dependent on external nutrients. B cells build their own supply.

Relevance for aging and immune function

During aging, the effectiveness of B cells declines. They respond more slowly to infections and produce less effective antibodies. Whether that partly stems from impaired metabolic reprogramming is still an open question. But the detailed map of what happens in healthy cells gives researchers a reference point for comparison with aged cells.

The findings may also eventually prove relevant to vaccine development and immunotherapy, both of which rely on stimulating B cell activation.

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