A new study published in Immunity describes the mechanism that drives B cells to mature into plasma cells. The research team found that B cell interaction with T follicular helper cells, another type of immune cell, influences B cell development into plasma cells instead of other cell types.
Antibody-producing plasma B cells are a key immune system component that fight viral infections and neutralize other foreign invaders. They are not that abundant, however, so a focus of vaccine development is to increase the number of plasma cells for better protection against infectious disease. Until now, what influences B cell precursors to become plasma B cells or to stay in germinal centers to be reprogrammed into other specific immune cell types was not well understood.
The research team looked at the markers being expressed on the surface of B cell precursors still located in germinal centers. They found that a subset of these precursor cells expressed Bcl6 at low levels and IRF4 at high levels. In addition, this subset of cells expressed the cellular marker, CD69. The team compared their gene sequences to known plasma B cells confirming they were indeed from the same cell group.
In addition, the team performed experiments to analyze the relationship between plasma B cells and T follicular helper cells which are known to be important for B cell maturation. It is known that T follicular helper cells stimulate B cells with CD40, a cell surface protein. The researchers engineered B cells that expressed low levels of CD40 and found that the number of plasma B cells greatly declined. Additional studies showed that strong interactions between the plasma B cell precursors and T follicular helper cells resulted in more precursors to mature into plasma B cells.
Tomohiro Kurosaki of the RIKEN Center for Integrative Medical Science, who led the study, says, "Understanding how the body generates high-affinity plasma B cells, which are important in fighting viral infections such as influenza, which kills around 1,000 people per year in Japan, is important for creating more powerful vaccinations. Our work has given us important insights into how these cells are produced, and we hope it will be useful in this effort."