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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo
Blood, Volume 118, No. 26, Year 2011
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Description
SCID resulting from mutations in IL2RG or JAK3 is characterized by lack of T and natural killer cells; B cells are present in normal number, but antibody responses are defective. Hematopoietic cell transplantation (HCT) is curative for SCID. However, B-cell dysfunction persists in a substantial proportion of patients. We hypothesized that impaired B-cell responses after HCT in IL2RG/JAK3 deficiency results from poor donor B-cell engraftment and defective γc-dependent cytokine signaling in host B cells. To test this, and to identify which γc cytokine(s) is critical for humoral immunity, we studied 28 transplanted patients with IL2RG/JAK3 deficiency. Lack of donor B-cell engraftment associated with persistent humoral dysfunction and significantly reduced memory B cells. B-cell proliferation induced by CD40L alone or together with CpG, anti-Ig, IL-4, IL-10, or IL-13 was comparable in healthy controls and in post-HCT SCID patients, irrespective of their chimerism status. However, in vitro stimulation with CD40L/IL-21 induced B-cell proliferation, plasmablast differentiation, and antibody secretion in patients with donor B cells, but not in patients with autologous B cells. These data imply that IL-21-mediated signaling is critical for long-lived humoral immunity and to restore antibody responses in IL2RG/JAK3-deficient patients after HCT. Furthermore, in vitro stimulation with CD40L/IL-21 can predict in vivo B-cell immunity in IL2RG/JAK3 SCID after transplantation. © 2011 by The American Society of Hematology.
Authors & Co-Authors
Recher, Mike
United States, Boston
Harvard Medical School
Berglund, Lucinda Jean
Australia, Sydney
Garvan Institute of Medical Research
Australia, Sydney
Unsw Sydney
Avery, Danielle T.
Australia, Sydney
Garvan Institute of Medical Research
Cowan, Morton J.
United States, San Francisco
Ucsf Benioff Children‘s Hospital
Gennery, Andrew R.
United Kingdom, Newcastle
University of Newcastle Upon Tyne, Faculty of Medical Sciences
Smart, Joanne M.
Australia, Melbourne
Royal Children's Hospital, Melbourne
Peake, Jane Elizabeth
Australia, Brisbane
Royal Children's Hospital Brisbane
Wong, Melanie
Australia, Sydney
The Children's Hospital at Westmead
Pai, Sung-yun
United States, Boston
Boston Children's Hospital
Baxi, Sachin N.
United States, Boston
Harvard Medical School
Walter, Jolán Eszter
United States, Boston
Massachusetts General Hospital
Palendira, Umaimainthan
Australia, Sydney
Garvan Institute of Medical Research
Australia, Sydney
Unsw Sydney
Tangye, Gillian A.
Australia, Sydney
Garvan Institute of Medical Research
Rice, Michael S.
Australia, Adelaide
Women's and Children's Hospital Adelaide
Brothers, Shannon
New Zealand, Auckland
Starship Children's Health
Al-Herz, Waleed
Kuwait
Al-sabah Hospital
Oettgen, Hans C.
United States, Boston
Harvard Medical School
Eibel, Hermann
Germany, Freiburg Im Breisgau
Universitätsklinikum Freiburg
Puck, Jennifer M.
United States, San Francisco
University of California, San Francisco
Cattaneo, Federica
Australia, Sydney
The Children's Hospital at Westmead
Ziegler, J. B.
Australia, Sydney
Sydney Children's Hospital, Randwick
Australia, Sydney
Unsw Sydney
Giliani, S.
Italy, Brescia
Università Degli Studi Di Brescia
Tangye, Stuart G.
Australia, Sydney
Garvan Institute of Medical Research
Australia, Sydney
Unsw Sydney
Notarangelo, Luigi Daniele
United States, Boston
Harvard Medical School
United States, Boston
Boston Children's Hospital
Statistics
Citations: 141
Authors: 24
Affiliations: 17
Identifiers
Doi:
10.1182/blood-2011-06-362533
ISSN:
00064971