In-depth characterization of CD24highCD38high transitional human B cells reveals different regulatory profiles

Abstract

CD24(high)CD38(high) transitional Bcells represent cells at a key stage in their developmental pathway. In addition, these Bcells 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 Bcells remains controversial. In this study we wanted to explore the regulatory properties of CD24(high)CD38(high) human Bcells. We used multicolor flow cytometry in combination with bioinformatics and functional studies to show that CD24(high)CD38(high) Bcells can be distinguished into multiple subsets with different regulatory functions. For the first time, the study reveals that human transitional Bcells encompass not only transitional type 1 and type 2Bcells, as previously suggested, but also distinct anergic type 3Bcells, as well as IL-10-producing CD27(+) transitional Bcells. Interestingly, the latter 2 subsets differentially regulate CD4(+) T-cell proliferation and polarization toward TH1 effector cells. Additional analyses reveal that the percentage of type 3Bcells is reduced and the frequency of CD27(+) transitional Bcells 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.