Quentin Simon1, Jacques-Olivier Pers1, Divi Cornec2, Laëtitia Le Pottier1, Rizgar A Mageed3, Sophie Hillion4. 1. EA2216, INSERM ESPRI, ERI29, Université de Brest, and LabEx IGO, Brest, France. 2. EA2216, INSERM ESPRI, ERI29, Université de Brest, and LabEx IGO, Brest, France; Rheumatology Department, CHRU Brest Morvan, Brest, France. 3. William Harvey Research Institute, Queen Mary University of London, London, United Kingdom. 4. EA2216, INSERM ESPRI, ERI29, Université de Brest, and LabEx IGO, Brest, France. Electronic address: sophie.hillion@univ-brest.fr.
Abstract
BACKGROUND: 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. OBJECTIVE: In this study we wanted to explore the regulatory properties of CD24(high)CD38(high) human B cells. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. OBJECTIVE: In this study we wanted to explore the regulatory properties of CD24(high)CD38(high) human B cells. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Authors: Guillermo Carvajal Alegria; Pierre Gazeau; Sophie Hillion; Claire I Daïen; Divi Y K Cornec Journal: Clin Rev Allergy Immunol Date: 2017-10 Impact factor: 8.667
Authors: Yannick Dieudonné; Vincent Gies; Aurélien Guffroy; Céline Keime; Anna K Bird; Jane Liesveld; Jennifer L Barnas; Vincent Poindron; Nawal Douiri; Pauline Soulas-Sprauel; Thierry Martin; Eric Meffre; Jennifer H Anolik; Anne-Sophie Korganow Journal: J Autoimmun Date: 2019-05-10 Impact factor: 7.094
Authors: Diego Catalán; Miguel Andrés Mansilla; Ashley Ferrier; Lilian Soto; Kristine Oleinika; Juan Carlos Aguillón; Octavio Aravena Journal: Front Immunol Date: 2021-04-29 Impact factor: 7.561
Authors: Victoria G Martin; Yu-Chang Bryan Wu; Catherine L Townsend; Grace H C Lu; Joselli Silva O'Hare; Alexander Mozeika; Anthonius C C Coolen; David Kipling; Franca Fraternali; Deborah K Dunn-Walters Journal: Front Immunol Date: 2016-12-02 Impact factor: 7.561