Researchers at Karolinska Institutet have mapped how so-called atypical B cells develop and change function over time. The study, published in The EMBO Journal, shows that the cells do not constitute a uniform group but instead follow several developmental pathways that converge on a common end stage. The findings may help explain why atypical B cells have previously been linked to different roles in the immune system.
B cells are an important part of the immune system and help the body recognise and fight infections. A group of B cells known as atypical B cells has attracted considerable interest among researchers in recent years. They occur in several infections, but also in connection with vaccinations and certain inflammatory diseases. Despite extensive research, it has long remained unclear how these cells arise and what function they serve.
In the new study, the researchers analysed blood samples from people who had experienced malaria as well as from healthy blood donors. By combining several advanced methods, they were able to track the development of individual B cells and examine how their properties changed over time.
Atypical B cells develop in several stages
The results show that atypical B cells are not a distinct cell type but rather exist along a continuum with early, intermediate and late developmental stages. The researchers identified three cell-surface markers, CD11c, CD24 and CD27, which made it possible to follow this progression.
"We show that atypical B cells can be understood as a continuous developmental process rather than as a fixed and clearly defined group of cells," says Christopher Sundling , researcher at the Department of Medicine, Solna , Karolinska Institutet, and corresponding author of the study.
The study also shows that the function of the cells changes as they develop. The early stages had a greater capacity to develop into antibody-producing cells and to produce cytokines, signalling molecules that help different parts of the immune system communicate with one another.
In the later stages, the cells instead acquired characteristics suggesting that they are better able to capture and present foreign substances to other immune cells. The researchers also found that the late-stage cells had a greater capacity to associate with microbial particles.
May have different origins
Another important observation was that atypical B cells may have several different origins. The researchers found evidence that they arise from different types of memory B cells that follow parallel developmental pathways but eventually reach a similar late stage.
"Our results show that the function of these cells changes gradually during development. 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 Alan-Dine Courey-Ghaouzi , doctoral student and first author of the study.
The researchers emphasise that the study was carried out in the context of malaria, but that the findings are likely to reflect general principles of how atypical B cells develop in other infections and inflammatory conditions as well.
The study was conducted in collaboration between researchers at Karolinska Institutet, Karolinska University Hospital, Umeå University, Emory University in the United States, Santa Lucia Foundation IRCCS in Italy and CK-CARE in Switzerland.
The research was funded by, among others, the Swedish Research Council, Karolinska Institutet, the Åke Wiberg Foundation, the Magnus Bergvall Foundation and Region Stockholm. The researchers report no conflicts of interest.
Publication
"Expression patterns of CD24 and CD27 resolve the origins and gradual differentiation of CD11c+ atypical memory B-cells after malaria infection" , Alan-Dine Courey-Ghaouzi, Linn Kleberg, Zaynab Mousavian, Maximilian Julius Lautenbach, Marta Pirronello, Ganesh E Phad, Mattias N E Forsell, Anna Färnert, Christopher Sundling, EMBO Journal, online 11 October 2026, doi:10.1038/s44318-026-00941-7
