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|Title:||B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans|
|Citation:||Journal of Experimental Medicine, 2010; 207(1):155-171|
|Publisher:||Rockefeller University Press|
|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.|
|Appears in Collections:||Medicine publications|
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