Alan-Dine Courey-Ghaouzi was hunched over a microscope in Solna, Sweden, tracking tiny immune cells that had long puzzled scientists. These cells, known as atypical B cells, appear during malaria, HIV, and even after vaccines—but no one knew exactly where they came from or what they truly did. Now, thanks to his team’s work at Karolinska Institutet, that mystery is beginning to unravel.
B cells are the body’s antibody factories, helping us fight off infections. But atypical B cells have always been a bit of a puzzle. Found in chronic infections and inflammatory diseases, they seemed to play multiple roles—sometimes helpful, sometimes not. Researchers debated whether they were a distinct cell type or just a temporary state. The new study, published in The EMBO Journal, shows they’re not a fixed group at all, but cells on a journey.
By analyzing blood from people who had recovered from malaria and comparing it to samples from healthy donors, the team mapped how these cells change over time. They discovered that atypical B cells develop in stages—early, intermediate, and late—guided by three surface markers: CD11c, CD27, and CD24. These markers act like license plates, letting scientists track each cell’s progress.
In the early stages, the cells are active producers—ready to turn into antibody-making factories and release cytokines, the immune system’s messaging chemicals. But as they mature, their role shifts. Late-stage cells lose that antibody potential and instead become skilled at grabbing foreign particles and showing them to other immune cells, like scouts handing over intel to commanders.
Even more surprising, these cells don’t all start from the same place. The researchers found evidence that different types of memory B cells—leftover soldiers from past infections—can each give rise to atypical B cells. These different origins follow parallel paths, but end up looking nearly identical.
“This may help explain why previous studies have described atypical B cells in different ways and assigned them different roles in the immune system,” says Courey-Ghaouzi, the study’s first author. The findings, while rooted in malaria research, likely apply to other long-term infections and immune challenges, from HIV to autoimmune diseases.
The study was a global effort, involving scientists from Karolinska Institutet, Karolinska University Hospital, Umeå University, Emory University in the U.S., Santa Lucia Foundation IRCCS in Italy, and CK-CARE in Switzerland. Understanding how these cells develop could one day help fine-tune vaccines or treat chronic inflammation.
Now, instead of seeing atypical B cells as a confusing contradiction, scientists can see them as part of a dynamic process—one that reveals how flexible and adaptable our immune system really is.