B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans

Avery, Danielle T., Deenick, Elissa K., Ma, Cindy S., Suryani, Santi, Simpson, Nicholas, Chew, Gary Y., Chan, Tyani D., Palendira, Umamainthan, Bustamante, Jacinta, Boisson-Dupuis, Stephanie, Choo, Sharon, Bleasel, Karl E., Peake, Jane, King, Cecile, French, Martyn A., Engelhard, Dan, Al-Hajjar, Sami, Al-Muhsen, Saleh, Magdorf, Klaus, Roesler, Joachim, Arkwright, Peter D., Hissaria, Pravin, Riminton, D. Sean, Wong, Melanie, Brink, Robert, Fulcher, David A., Casanova, Jean Laurent, Cook, Mathew C. and Tangye, Stuart G. (2010) B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans. Journal of Experimental Medicine, 207 1: 155-171. doi:10.1084/jem.20091706

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Author Avery, Danielle T.
Deenick, Elissa K.
Ma, Cindy S.
Suryani, Santi
Simpson, Nicholas
Chew, Gary Y.
Chan, Tyani D.
Palendira, Umamainthan
Bustamante, Jacinta
Boisson-Dupuis, Stephanie
Choo, Sharon
Bleasel, Karl E.
Peake, Jane
King, Cecile
French, Martyn A.
Engelhard, Dan
Al-Hajjar, Sami
Al-Muhsen, Saleh
Magdorf, Klaus
Roesler, Joachim
Arkwright, Peter D.
Hissaria, Pravin
Riminton, D. Sean
Wong, Melanie
Brink, Robert
Fulcher, David A.
Casanova, Jean Laurent
Cook, Mathew C.
Tangye, Stuart G.
Title B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans
Journal name Journal of Experimental Medicine   Check publisher's open access policy
ISSN 0022-1007
Publication date 2010-01-18
Sub-type Article (original research)
DOI 10.1084/jem.20091706
Open Access Status File (Publisher version)
Volume 207
Issue 1
Start page 155
End page 171
Total pages 7
Place of publication New York , NY, United States
Publisher Rockefeller University Press
Language eng
Formatted abstract
Engagement of cytokine receptors by specific ligands activate Janus kinase-signal transducer and activator of transcription (STAT) signaling pathways. The exact roles of STATs in human lymphocyte behavior remain incompletely defined. Interleukin (IL)-21 activates STAT1 and STAT3 and has emerged as a potent regulator of B cell differentiation. We have studied patients with inactivating mutations in STAT1 or STAT3 to dissect their contribution to B cell function in vivo and in response to IL-21 in vitro. STAT3 mutations dramatically reduced the number of functional, antigen (Ag)-specific memory B cells and abolished the ability of IL-21 to induce naive B cells to differentiate into plasma cells (PCs). This resulted from impaired activation of the molecular machinery required for PC generation. In contrast, STAT1 deficiency had no effect on memory B cell formation in vivo or IL-21-induced immunoglobulin secretion in vitro. Thus, STAT3 plays a critical role in generating effector B cells from naive precursors in humans. STAT3-activating cytokines such as IL-21 thus underpin Ag-specific humoral immune responses and provide a mechanism for the functional antibody deficit in STAT3-deficient patients.
Keyword Hyper-IGE syndrome
Secreting Cells
Cutting Edge
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Wed, 07 Mar 2012, 01:30:45 EST by Melanie Thomas on behalf of School of Medicine