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https://hdl.handle.net/2440/89063
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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 1540-9538 |
Statement of Responsibility: | 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. |
DOI: | 10.1084/jem.20091706 |
Published version: | http://dx.doi.org/10.1084/jem.20091706 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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