A new cellular atlas reveals the maturation process of human B cells and their involvement in a type of leukemia

Researchers at Cima Universidad de Navarra, in collaboration with scientists from Navarrabiomed and international groups, have compiled the most comprehensive atlas to date on the differentiation of human B cells, a type of white blood cell essential for defending against infections. The dysregulation of these cells is implicated in various hematological diseases, such as acute lymphoblastic leukemia, so this resource could improve the diagnosis and treatment of patients with this pathology.

The study accurately describes eight cell subtypes obtained from healthy donors and offers a unique resource for understanding, at the molecular level, how this process progresses in humans. "In our study, we isolated these cell populations using state-of-the-art flow cytometry and performed a combined analysis using ‘omic’ techniques. On the one hand, we used transcriptomics to find out which genes are activated at each stage, and on the other, ATAC-seq, a technique that reveals which regions of DNA are accessible, indicating where the factors that regulate gene expression can act," explains Núria Planell, postdoctoral researcher at Cima's Machine Learning in Biomedicine Group and first author of the study, conducted at the Cancer Center Clínica Universidad de Navarra.

The combined analysis of both “omics” allowed us to reconstruct the regulatory network that controls B cell maturation and reveal which genes are key in each step of the process. “In collaboration with King Abdullah University of Science and Technology (KAUST) in Saudi Arabia, we increased the sequencing depth of ATAC-seq in order to improve the resolution in identifying transcription factor binding sites,” he adds. The results have been published in the scientific journal Science Advances.

Application in patients

The atlas developed at Cima offers potential application in hematological diseases, especially B-cell acute lymphoblastic leukemia (B-ALL), a cancer that arises when lymphoblasts—immature stages of B cells—fail to differentiate properly.

The study analyzed 500 samples from patients with this type of leukemia, obtained from public databases, and compared their profiles with the atlas generated from healthy donors. "We have been able to identify the exact point in the maturation process at which each patient's cells become blocked. In addition, we have found that certain genetic subtypes of B-ALL are associated with earlier or more advanced stages of cell differentiation, which could have an impact on the clinical response to certain treatments. Although these advances still require experimental validation, the resource generated represents an essential first step in translating basic knowledge into the medical field. “The ultimate goal would be to design new therapeutic strategies focused on the key regulators identified for each subtype of the disease,” concludes the Cima researcher.

The work, carried out within the framework of the CIBER Cancer Network (CIBERONC), has received public funding from the Ministry of Science and Innovation and support from institutions such as the Myeloma Multiple Research Foundation, the “la Caixa” Foundation, and the Spanish Association Against Cancer.

Bibliographic reference

Science Advances. 2025 Oct 10;11(41):eadw3110. doi: 10.1126/sciadv.adw3110. Epub 2025 Oct 10.
•    Uncovering the regulatory landscape of early human B cell lymphopoiesis and its implications in the pathogenesis of B-ALL