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.2015-02-032015-02-032010Journal of Experimental Medicine, 2010; 207(1):155-1710022-10071540-9538http://hdl.handle.net/2440/89063Engagement 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.en© 2010 Avery et al.Plasma CellsHumansImmunoglobulinsInterleukinsAntigensSignal TransductionCell DifferentiationAntibody FormationImmunologic MemoryTime FactorsSTAT1 Transcription FactorSTAT3 Transcription FactorInterleukin-21Journal article002010015010.1084/jem.200917060002736908000142-s2.0-7614913941933766