A Secret Handshake Determines B-Cell Fate

The strength of the interaction between B-cells and T follicular helper cells decides whether the B-cells become antibody-producing plasma cells, researchers say.

AsianScientist (May 3, 2018) – A team of scientists from RIKEN and Osaka University, Japan, have discovered a mechanism that governs how B-cells are chosen to become plasma cells that produce antibodies against infections. Their findings are published in Immunity.

Plasma cells, which move through the body releasing antibodies, are an important component of the body’s fight against viral infections and other invaders. They are relatively rare, however, and increasing their ranks is a major goal of vaccination.

Scientists do not fully understand how precursor cells are selected either to enter the body’s fluids as plasma B-cells or to remain in germinal centers where they undergo reprogramming to become more specific attackers against infection.

In this study, a group of researchers led by Dr. Tomohiro Kurosaki of RIKEN in Japan has discovered that the strength of the interaction between the B-cells and another type of immune cell, called T follicular helper cells, determines whether B-cells become plasma cells.

It is known that plasma cells express a transcription factor called IRF4, and conversely do not express a transcription factor called Bcl6. The researchers wondered whether the fate of the cells was already being determined while they were in the germinal centers within lymph nodes and the spleen, where B-cells mature.

They examined the expression of these two factors in B-cells still located in germinal centers, and found that in a subset of cells, Bcl6 was expressed at a low level and IRF4 at a high level. They also found that these cells express a cellular marker called CD69.

To determine whether the cells they had identified were indeed precursors to plasma cells, they compared them with germinal center-derived plasma cells. It became clear that these cells shared the same developmental features with germinal center-derived plasma cells, suggesting that they were indeed precursors.

Lastly, the researchers examined the relationship between these precursor cells and T follicular helper cells, which are important for the maturation of B-cells. Since the T follicular helper cells stimulate B-cells with a surface protein called CD40, the team created B-cells that expressed CD40 at low levels.

They found that the number of plasma cells dropped dramatically. Further experiments showed that the strength of the interaction between the plasma cell precursors and the T follicular helper cells determines whether the B-cell precursors are chosen to be plasma cells or to remain in the germinal center to undergo further maturation into a high-affinity plasma cell.

“Understanding how the body generates high-affinity plasma B-cells, which are important in fighting viral infections such as influenza is important for creating more powerful vaccinations. Our work has given us important insights into how these cells are produced,” said Kurosaki.

The article can be found at: Ise et al. (2018) T Follicular Helper Cell-Germinal Center B Cell Interaction Strength Regulates Entry into Plasma Cell or Recycling Germinal Center Cell Fate.


Source: RIKEN; Photo: Shutterstock.
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