How proteins guide plasma cells to bone marrow for long-term immunity

Vaccine effectiveness relies on creating a strong antibody response that can be reactivated to fight future infections. Now, researchers from Japan report that antibody-producing cells are destined for longevity from the moment they are born.

In a study published in the Journal of Experimental Medicine, a multi-institutional research team led by Osaka University reveals that a key cell population involved in long-term immunity to infection is programmed early in its lifecycle to travel to protected sites in the body.

Plasma cells originate in lymphoid (immune) tissues and then migrate to protected sites throughout the body, where they produce large amounts of antibodies in response to infection-related substances. Long-lived plasma cells (LLPCs), which are important for protection from reinfection, are thought to migrate specifically to the bone marrow.

“The importance of LLPCs to immunity is well known,” says Wataru Ise, lead author of the study. “However, it is unclear how plasma cells generated in lymphoid tissues migrate to the bone marrow, where they can survive for a long time.”

To investigate this, the researchers looked at the different types of proteins expressed by plasma cells that had just been produced by lymphoid tissues compared with the proteins expressed by plasma cells that successfully made it to the bone marrow.

“The results were very clear,” explains Tomohiro Kurosaki, senior author. “We found that high expression of a single protein called integrin β7 was an excellent marker for plasma cells migrating to the bone marrow.”

When the researchers explored how integrin β7^hi cells could home to the right location, they found that these cells also express high levels of the transcription factor KLF2, which prompts them to move out of lymphoid tissue and into the blood. Importantly, decreased expression of the gene encoding KLF2 or its target S1pr1, reduced the ability of mice to develop resistance to flu.

“Our findings show that the migration program of plasma cells is established in their tissue of origin and plays a critical role in determining the durability of the antibody response,” says Ise.

Given that a durable antibody response is key to vaccine effectiveness, the findings from this study could be used to improve vaccines. Promoting plasma cell migration and survival in protected sites like the bone marrow could mean establishing lasting immunity to dangerous infections.

Vaccine effectiveness relies on creating a strong antibody response that can be reactivated to fight future infections. Now, researchers from Japan report that antibody-producing cells are destined for longevity from the moment they are born.

In a study published in the Journal of Experimental Medicine, a multi-institutional research team led by Osaka University reveals that a key cell population involved in long-term immunity to infection is programmed early in its lifecycle to travel to protected sites in the body.

Plasma cells originate in lymphoid (immune) tissues and then migrate to protected sites throughout the body, where they produce large amounts of antibodies in response to infection-related substances. Long-lived plasma cells (LLPCs), which are important for protection from reinfection, are thought to migrate specifically to the bone marrow.

“The importance of LLPCs to immunity is well known,” says Wataru Ise, lead author of the study. “However, it is unclear how plasma cells generated in lymphoid tissues migrate to the bone marrow, where they can survive for a long time.”

To investigate this, the researchers looked at the different types of proteins expressed by plasma cells that had just been produced by lymphoid tissues compared with the proteins expressed by plasma cells that successfully made it to the bone marrow.

“The results were very clear,” explains Tomohiro Kurosaki, senior author. “We found that high expression of a single protein called integrin β7 was an excellent marker for plasma cells migrating to the bone marrow.”

When the researchers explored how integrin β7^hi cells could home to the right location, they found that these cells also express high levels of the transcription factor KLF2, which prompts them to move out of lymphoid tissue and into the blood. Importantly, decreased expression of the gene encoding KLF2 or its target S1pr1, reduced the ability of mice to develop resistance to flu.

“Our findings show that the migration program of plasma cells is established in their tissue of origin and plays a critical role in determining the durability of the antibody response,” says Ise.

Given that a durable antibody response is key to vaccine effectiveness, the findings from this study could be used to improve vaccines. Promoting plasma cell migration and survival in protected sites like the bone marrow could mean establishing lasting immunity to dangerous infections.