Trace the pathway to immunity, cell by cell at a time

Vaccines work effectively by creating long-lived immune cells, often more than decades. These immune cells create a protective barrier that can prevent or minimize reinfection, and memories allow us to recognize an old invader like a virus and destroy it before it causes disease. Antibodies in our blood are a barrier created by “long-lived plasma cells” and although the importance of these cells has always been known, how and when they are made after vaccination remains a mystery so far.

A research team led by Dr. Marcus Robinson and Professor David Tarlinton from Monash University’s Immunological Memory Laboratory has shown in real time how immunological memory works. cell stored in the bone marrow at about one unicellular every hour for several weeks after vaccination. Their work has been published in Science of Immunology.

The researchers used a genetic system in mice to map the gradual accumulation of these cells. This system, called timestamps, allows researchers to indelibly mark all plasma cells present at a certain time after vaccination and then return later and identify those that have survived and therefore have lived long. By doing this regularly after vaccination, the researchers revealed the accumulation history of these long-lived cells, pinpointing when they were made and where they went.

After we are immunized, we remain largely immune to the disease because our bodies provide a constant supply of antibodies against the vaccinated disease — essentially ensuring that we adequate supply of these antibodies. We have identified sites in the body where these long-lived plasma cells are generated (including lymph nodes, tonsils and intestines). But how some vaccines cause these cells to last for decades versus those that disappear after a few months is unknown. Due to global interest in the long-term immunity provided by COVID vaccines, it is increasingly urgent to understand this process.

Using a mouse model, the researchers demonstrated a fluorescent protein (called the TdTomato protein) only in specific cells that produce antibodies against a particular vaccine. Because these cells fluoresce, it is possible to monitor individual cells when they are manufactured and where they are stored.

The researchers also used a range of tools to identify only those plasma cells produced by the vaccine. All plasma cells in mouse model express the protein TdTomato, and among them, they identified proteins that recognize vaccines. Finally, using timestamps, they know when those cells were made and therefore how old they are.

According to Professor Tarlinton, studying these individual cells as they are born, mature and stored to protect us against repeated invasion by a particular virus or bacteria “has a potential to help protect us against repeated invasions by a particular virus or bacteria” could inform our understanding of how long-lived plasma cells are recruited.”

The complexity of the study has allowed the researchers to identify other aspects of specific immunity building:

• How do these plasma cells enter the bone marrow?
• Will these plasma cells have to replace other cells when they are stored in areas like the bone marrow?
• Or if these cells “find” a niche vacated by previous plasma cells, either die or move elsewhere.

Mapping of these cells showed that a specific vaccination in mice resulted in the generation of approximately 40,000 plasma cells persistently in bone marrow. These cells, after initial growth, then decline at a rate of about 0.1% a day with a half-life of about 700 days, providing both an estimate of the protective and deterministic time for research. delve deeper into the long-lived cells themselves.

According to Professor Tarlinton, understanding the plasma Generated, live and die cells “will inform our ability to regulate their recruitment, through different vaccine combinations or delivery strategies – ultimately enabling we can increase the lifespan of immunity,” he said.

“In fact, there is an interesting work recently reported in Nature describe how altering the vaccination mechanism can significantly affect the character of the immune response, and we will anticipate the production of these particular cells that are at the heart of their work. I. ”