CD24^highCD38^high transitional B cells represent cells at a key stage in their developmental pathway. In addition, these B cells have been widely ascribed regulatory functions and involvement in the control of chronic inflammatory diseases. However, the phenotypic and functional overlap between these cells and regulatory B cells remains controversial.

In this study we wanted to explore the regulatory properties of CD24^highCD38^high human B cells.

We used multicolor flow cytometry in combination with bioinformatics and functional studies to show that CD24^highCD38^high B cells can be distinguished into multiple subsets with different regulatory functions.

For the first time, the study reveals that human transitional B cells encompass not only transitional type 1 and type 2 B cells, as previously suggested, but also distinct anergic type 3 B cells, as well as IL-10–producing CD27⁺ transitional B cells. Interestingly, the latter 2 subsets differentially regulate CD4⁺ T-cell proliferation and polarization toward T_H1 effector cells. Additional analyses reveal that the percentage of type 3 B cells is reduced and the frequency of CD27⁺ transitional B cells is increased in patients with autoimmune diseases compared with those in matched healthy subjects.

This study provides evidence for the existence of different transitional B-cell subsets, each displaying unique phenotypic and regulatory functional profiles. Furthermore, the study indicates that altered distribution of transitional B-cell subsets highlights different regulatory defects in patients with different autoimmune diseases.