B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans
dc.contributor.author | Avery, Danielle T | |
dc.contributor.author | Deenick, Elissa | |
dc.contributor.author | Ma, Cindy | |
dc.contributor.author | Suryani, Santi | |
dc.contributor.author | Simpson, Nick | |
dc.contributor.author | Chew, Gary | |
dc.contributor.author | Chan, Tyani | |
dc.contributor.author | Palendira, Umamainthan | |
dc.contributor.author | Bustamante, Jacinta | |
dc.contributor.author | Boisson-Dupuis, Stephanie | |
dc.contributor.author | Choo, Sharon | |
dc.contributor.author | Bleasel, Karl E. | |
dc.contributor.author | Cook, Matthew | |
dc.contributor.author | Arkwright, Peter D | |
dc.date.accessioned | 2015-12-07T22:44:26Z | |
dc.date.issued | 2010 | |
dc.date.updated | 2016-06-14T08:35:07Z | |
dc.description.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. | |
dc.identifier.issn | 0022-1007 | |
dc.identifier.uri | http://hdl.handle.net/1885/25186 | |
dc.publisher | Rockefeller University Press | |
dc.source | Journal of Experimental Medicine | |
dc.subject | Keywords: immunoglobulin; interleukin 21; interleukin 21 receptor; STAT1 protein; STAT3 protein; antibody response; antigen specificity; article; B lymphocyte; B lymphocyte differentiation; controlled study; effector cell; gene inactivation; gene mutation; human; h | |
dc.title | B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans | |
dc.type | Journal article | |
local.bibliographicCitation.issue | 1 | |
local.bibliographicCitation.lastpage | 171 | |
local.bibliographicCitation.startpage | 155 | |
local.contributor.affiliation | Avery, Danielle T, Garvan Institute of Medical Research | |
local.contributor.affiliation | Deenick, Elissa, Garvan Institute of Medical Research | |
local.contributor.affiliation | Ma, Cindy, Garvan Institute of Medical Research | |
local.contributor.affiliation | Suryani, Santi, Garvan Institute of Medical Research | |
local.contributor.affiliation | Simpson, Nick, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Chew, Gary, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Chan, Tyani, Garvan Institute of Medical Research | |
local.contributor.affiliation | Palendira, Umamainthan, Garvan Institute of Medical Research | |
local.contributor.affiliation | Bustamante, Jacinta, Necker Medical School, University of Paris Descartes | |
local.contributor.affiliation | Boisson-Dupuis, Stephanie, Necker Medical School, University of Paris Descartes | |
local.contributor.affiliation | Choo, Sharon, Royal Childrens' Hospital Melbourne | |
local.contributor.affiliation | Bleasel, Karl E., Royal Melbourne Hospital | |
local.contributor.affiliation | Cook, Matthew, College of Medicine, Biology and Environment, ANU | |
local.contributor.affiliation | Arkwright, Peter D, University of Manchester | |
local.contributor.authoremail | u2572788@anu.edu.au | |
local.contributor.authoruid | Simpson, Nick, u4189573 | |
local.contributor.authoruid | Chew, Gary, u3562042 | |
local.contributor.authoruid | Cook, Matthew, u2572788 | |
local.description.embargo | 2037-12-31 | |
local.description.notes | Imported from ARIES | |
local.identifier.absfor | 110799 - Immunology not elsewhere classified | |
local.identifier.ariespublication | f2965xPUB37 | |
local.identifier.citationvolume | 207 | |
local.identifier.doi | 10.1084/jem.20091706 | |
local.identifier.scopusID | 2-s2.0-76149139419 | |
local.identifier.thomsonID | 000273690800014 | |
local.identifier.uidSubmittedBy | f2965 | |
local.type.status | Published Version |
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