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

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dc.contributor.authorAvery, D.
dc.contributor.authorDeenick, E.
dc.contributor.authorMa, C.
dc.contributor.authorSuryani, S.
dc.contributor.authorSimpson, N.
dc.contributor.authorChew, G.
dc.contributor.authorChan, T.
dc.contributor.authorPalendira, U.
dc.contributor.authorBustamante, J.
dc.contributor.authorBoisson-Dupuis, S.
dc.contributor.authorChoo, S.
dc.contributor.authorBleasel, K.
dc.contributor.authorPeake, J.
dc.contributor.authorKing, C.
dc.contributor.authorFrench, M.
dc.contributor.authorEngelhard, D.
dc.contributor.authorAl-Hajjar, S.
dc.contributor.authorAl-Muhsen, S.
dc.contributor.authorMagdorf, K.
dc.contributor.authorRoesler, J.
dc.contributor.authoret al.
dc.date.issued2010
dc.description.abstractEngagement 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.description.statementofresponsibilityDanielle T. Avery ... Pravin Hissaria ... Melanie Wong ... et al.
dc.identifier.citationJournal of Experimental Medicine, 2010; 207(1):155-171
dc.identifier.doi10.1084/jem.20091706
dc.identifier.issn0022-1007
dc.identifier.issn1540-9538
dc.identifier.urihttp://hdl.handle.net/2440/89063
dc.language.isoen
dc.publisherRockefeller University Press
dc.rights© 2010 Avery et al.
dc.source.urihttps://doi.org/10.1084/jem.20091706
dc.subjectPlasma Cells
dc.subjectHumans
dc.subjectImmunoglobulins
dc.subjectInterleukins
dc.subjectAntigens
dc.subjectSignal Transduction
dc.subjectCell Differentiation
dc.subjectAntibody Formation
dc.subjectImmunologic Memory
dc.subjectTime Factors
dc.subjectSTAT1 Transcription Factor
dc.subjectSTAT3 Transcription Factor
dc.subjectInterleukin-21
dc.titleB cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans
dc.typeJournal article
pubs.publication-statusPublished

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