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Type: Journal article
Title: B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans
Author: Avery, D.
Deenick, E.
Ma, C.
Suryani, S.
Simpson, N.
Chew, G.
Chan, T.
Palendira, U.
Bustamante, J.
Boisson-Dupuis, S.
Choo, S.
Bleasel, K.
Peake, J.
King, C.
French, M.
Engelhard, D.
Al-Hajjar, S.
Al-Muhsen, S.
Magdorf, K.
Roesler, J.
et al.
Citation: Journal of Experimental Medicine, 2010; 207(1):155-171
Publisher: Rockefeller University Press
Issue Date: 2010
ISSN: 0022-1007
Statement of
Danielle T. Avery ... Pravin Hissaria ... Melanie Wong ... et al.
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.
Keywords: Plasma Cells; Humans; Immunoglobulins; Interleukins; Antigens; Signal Transduction; Cell Differentiation; Antibody Formation; Immunologic Memory; Time Factors; STAT1 Transcription Factor; STAT3 Transcription Factor
Rights: © 2010 Avery et al.
RMID: 0020100150
DOI: 10.1084/jem.20091706
Appears in Collections:Medicine publications

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