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

• Published in: Journal of allergy and clinical immunology Vol. 137; no. 5; pp. 1577 - 1584.e10
• Main Authors: Simon, Quentin, Pers, Jacques-Olivier, Cornec, Divi, Le Pottier, Laëtitia, Mageed, Rizgar A., Hillion, Sophie
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.05.2016; Elsevier
• Subjects: autoimmunity; chronic inflammatory diseases; immune regulation; Immunology; Life Sciences; Transitional B cells; chronic inflammatory diseases; MNC; PC5; KO; Breg; PLCγ2; SLE; Transitional B cells; immune regulation; FLOCK; BCR; MFI; pSS; FITC; PB; SPADE; autoimmunity; APC; PE; HC; T1; T2; T3
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2015.09.014

CD24highCD38high 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 CD24highCD38high human B cells. We used multicolor flow cytometry in combination with bioinformatics and functional studies to show that CD24highCD38high 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 TH1 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.