Bach2 Is Needed for Immune Cells to Become Memory B Cells

A new study by researchers at Osaka University shows that our body’s ability to respond to re-infection requires Bach2, a protein that regulates the expression of genes needed to instruct activated B cells under selection to become memory B cells. Their results were published in the Journal of Experimental Medicine. 

The team focused their research on understanding what causes activated B cells to become memory B cells, plasma cells, or to be recycled. On the basis of specific markers, the researchers identified a subset of B cells that they determined were prone to become memory B cells, which they called pro-memory B cells. 

They then examined mice lacking the protein Bach2, a transcription factor required for memory B cell production. These mice are known to be deficient in producing memory B cells. The researchers found that the lack of Bach2 was associated with fewer pro-memory B cells and increased expression of genes related to a protein complex called mTORC1.

Further testing showed the importance of mTORC1. "We ultimately found that mTORC1 signaling was less active in pro-memory B cells than in those that ended up being recycled," says lead researcher Tomohiro Kurosaki. Inhibiting mTORC1 activity in the Bach2 knockout mice allowed them to produce memory B cells. Additionally, in wild-type mice, artificially reducing mTORC1 activity in B cells led to the production of more memory B cells than normal, while increasing its activity had the opposite effect. However, mTORC1 activity alone could not explain everything. Experiments showed that the unique combination of Bach2 expression and reduced mTORC1 activity is necessary to become memory B cells.

Understanding the process through which memory B cells are produced means that this process can be manipulated for our benefit. "Given the importance of memory B cells in protecting us against re-infection, being able to induce their production could be helpful for developing efficient vaccines that remain effective for years," concludes Kurosaki.