IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo

Recher, Mike, Berglund, Lucinda J., Avery, Danielle T., Cowan, Morton J., Gennery, Andrew R., Smart, Joanne, Peake, Jane, Wong, Melanie, Pai, Sung-Yun, Baxi, Sachin, Walter, Jolan E., Palendir, Umaimainthan, Tangye, Gillian A., Rice, Michael, Brothers, Shannon, Al-Herz, Waleed, Oettgen, Hans, Eibel, Hermann, Puck, Jennifer M., Cattaneo, Federica, Ziegler, John B., Giliani, Silvia, Tangye, Stuart G. and Notarangelo, Luigi D. (2011) IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo. Blood, 118 26: 6824-6835. doi:10.1182/blood-2011-06-362533

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Author Recher, Mike
Berglund, Lucinda J.
Avery, Danielle T.
Cowan, Morton J.
Gennery, Andrew R.
Smart, Joanne
Peake, Jane
Wong, Melanie
Pai, Sung-Yun
Baxi, Sachin
Walter, Jolan E.
Palendir, Umaimainthan
Tangye, Gillian A.
Rice, Michael
Brothers, Shannon
Al-Herz, Waleed
Oettgen, Hans
Eibel, Hermann
Puck, Jennifer M.
Cattaneo, Federica
Ziegler, John B.
Giliani, Silvia
Tangye, Stuart G.
Notarangelo, Luigi D.
Title IL-21 is the primary common γ chain-binding cytokine required for human B-cell differentiation in vivo
Journal name Blood   Check publisher's open access policy
ISSN 0006-4971
Publication date 2011-12-22
Sub-type Article (original research)
DOI 10.1182/blood-2011-06-362533
Volume 118
Issue 26
Start page 6824
End page 6835
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society of Hematology
Collection year 2012
Language eng
Formatted abstract
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.
Keyword Cell Differentiation
Flow cytometry
Hematopoietic Stem
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 46 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 14 Mar 2012, 10:10:59 EST by Melanie Thomas on behalf of Paediatrics & Child Health - RBWH