Our immune system relies on a stable set of antibodies that barely changes over time

A small group of antibodies in your blood stays the same for years, even after vaccines. A group of scientists from Utrecht University and their international collaborators report this discovery in Science Advances. These stable antibodies create a unique and personal immune "fingerprint" that barely changes over time. The discovery helps explain how long-term immunity works, and it may guide future vaccines to provide better and longer-lasting protection.

While our bodies constantly produce new antibodies to fight off infections, much of our immune system stays surprisingly unchanged. It turns out that our long-term protection largely depends on a small group of cells that continuously produce the same antibodies, year after year. These cells are located deep in the bone marrow and act like precise copy machines, always making identical antibodies.

Exactly the same

The researchers discovered this by analysing blood samples from eleven volunteers over the course of one year. During that time, all participants received three COVID-19 vaccinations.

What the researchers found was unexpected. Despite the immune system being triggered by the vaccinations, the main group of antibodies in each person’s blood remained exactly the same in type, amount, and structure.

Our immune system relies on a stable group of antibody-producing cells, located in the bone marrow, that stay active for many years

“That was a real eye-opener,” says Danique van Rijswijck, molecular biologist and lead author of the study. “The most common antibodies we saw were often exactly the same throughout the year. New antibodies formed after vaccination barely showed up in the overall picture. This means the immune system relies on a stable group of antibody-producing cells, located in the bone marrow, that stay active for many years.”

Biologist Albert Bondt, co-leader of the research, adds: “Each participant had a unique set of highly present antibodies, like an immune fingerprint. That pattern stayed nearly unchanged throughout the year.”

‘Copy machines’ in the bone marrow

Antibodies are proteins that recognize and neutralize viruses and bacteria. They’re made by plasma cells, which are a type of white blood cell. Some plasma cells are short-lived, but others live much longer. These long-lived plasma cells settle in the bone marrow and keep producing the same antibodies for years. It’s as if there are tiny ‘copy machines’ in your bone marrow, printing the same page over and over again, says Van Rijswijck.

Ultra-sensitive technology

This discovery was made possible thanks to highly sensitive equipment in the lab of Bondt and Van Rijswijck. Their team was able to measure antibodies in such detail that even the smallest differences in chemical composition could be detected. This allowed them to see that many of the most common antibodies had exactly the same mass throughout the year — meaning they came from the same long-lived cells.

Lasting versus short-term immunity

This research helps solve a key question: why does protection from some infections, like measles, last a lifetime, while immunity to others, like flu or COVID-19, fades more quickly? The answer may lie in which plasma cells become long-lived and keep producing antibodies.

If we can understand why some plasma cells live longer than others, we may be able to design vaccines that specifically activate those cells

“If we can understand why some plasma cells live longer than others, we may be able to design vaccines that specifically activate those cells,” says Van Rijswijck. “That could mean that, in the future, just one vaccination may be enough for long-term protection. This could even be the case for diseases that now require multiple doses.”

Interpreting blood tests differently

The findings also suggest that doctors might need to rethink how they interpret antibody levels in blood tests. “A high level of antibodies doesn't necessarily mean someone was recently infected or vaccinated,” says Bondt. “It could simply mean they have a lot of long-lived antibodies that have been circulating for years.”

A high level of antibodies doesn't necessarily mean someone was recently infected or vaccinated

Although this research answers important questions, it also raises new ones. What exactly causes a plasma cell to become long-lived? Can we control that process? And what are these stable antibodies actually targeting?

Allergies and autoimmune diseases

To find answers, the researchers plan to look more closely at how different vaccines influence immune responses. They also want to understand why some antibodies become part of the stable ‘fingerprint’ while others don’t. Another research goal is to explore whether these long-lasting antibodies could play a role in allergies or autoimmune diseases.

“The fact that our blood contains such large amounts of antibodies that remain stable for years is already an important discovery,” says Van Rijswijck. “But it also opens the door to more targeted and long-lasting ways of boosting our immune system.”