In-depth characterization of CD24(high)CD38(high) transitional human B cells reveals different regulatory profiles

• Published in: Journal of allergy and clinical immunology 2016-05, Vol.137 (5), p.1577-1584.e10
• Main Authors: Simon, Quentin, Pers, Jacques-Olivier, Cornec, Divi, Le Pottier, Laëtitia, Mageed, Rizgar A, Hillion, Sophie
• Format: Article
• Language: English
• Subjects: ADP-ribosyl Cyclase 1 - immunology; Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid - immunology; CD24 Antigen - immunology; Cytokines - immunology; Female; Graft Rejection - immunology; HIV Infections - immunology; Humans; Immunology; Kidney Transplantation; Life Sciences; Lupus Erythematosus, Systemic - immunology; Male; Membrane Glycoproteins - immunology; Middle Aged; Precursor Cells, B-Lymphoid - immunology; Sjogren's Syndrome - immunology
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2015.09.014

CD24(high)CD38(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(high)CD38(high) human B cells. We used multicolor flow cytometry in combination with bioinformatics and functional studies to show that CD24(high)CD38(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 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.