IL-21 signalling via STAT3 primes human naïve B cells to respond to IL-2 to enhance their differentiation into plasmablasts

Author:

Berglund Lucinda J.123,Avery Danielle T.1,Ma Cindy S.12,Moens Leen1,Deenick Elissa K.12,Bustamante Jacinta456,Boisson-Dupuis Stephanie47,Wong Melanie8,Adelstein Stephen9,Arkwright Peter D.10,Bacchetta Rosa11,Bezrodnik Liliana12,Dadi Harjit13,Roifman Chaim M.13,Fulcher David A.3,Ziegler John B.14,Smart Joanne M.15,Kobayashi Masao16,Picard Capucine456,Durandy Anne5617,Cook Matthew C.181920,Casanova Jean-Laurent467,Uzel Gulbu21,Tangye Stuart G.12

Affiliation:

1. Immunology Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia;

2. St Vincent’s Clinical School, University of New South Wales, Australia;

3. Department of Immunology, Institute of Clinical Pathology and Medical Research, Westmead Hospital, Westmead, NSW, Australia;

4. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U980, Necker Medical School, University Paris Descartes, Paris, France;

5. Study Center for Primary Immunodeficiencies, AP-HP, Necker Hospital, Paris, France;

6. Université Paris Descartes, Institut Imagine, Paris, France;

7. Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, NY;

8. Department of Immunology, Children’s Hospital at Westmead, Westmead, NSW, Australia;

9. Clinical Immunology, Royal Prince Alfred Hospital, Sydney, NSW, Australia;

10. University of Manchester, Royal Manchester Children’s Hospital, Manchester, United Kingdom;

11. San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), San Raffaele Scientific Institute, Milan, Italy;

12. Immunology Unit, Ricardo Gutiérrez Children Hosptial, Ciudad Autónoma de Buenos Aires, Argentina;

13. Canadian Centre for Primary Immunodeficiency, Hospital for Sick Children and University of Toronto, Toronto, ON, Canada;

14. Department of Immunology, Sydney Children's Hospital, Randwick, NSW, Australia and School of Women’s and Children’s Health, University of NSW, Randwick, Australia;

15. Department of Allergy and Immunology, Royal Children’s Hospital Melbourne, Melbourne, VIC, Australia;

16. Department of Pediatrics, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan;

17. INSERM, Unité U768, Hôpital Necker Enfants-Malades, Paris, France;

18. Australian National University Medical School, and

19. John Curtin School of Medical Research, Australian National University, ACT, Canberra, Australia;

20. Department of Immunology, The Canberra Hospital, Canberra, ACT, Australia; and

21. Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD

Abstract

Key Points IL21-mediated induction of CD25 expression on naïve human B cells requires STAT3. A lack of response to IL-2 may amplify humoral immunodeficiency in patients with STAT3, IL2RG, or IL21R mutations due to unresponsiveness to IL21.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference50 articles.

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