B cell-intrinsic signaling through IL-21 receptor and STAT3 is required for establishing long-lived antibody responses in humans
| Autor: | Jane Peake, Danielle T. Avery, Umamainthan Palendira, Martyn A. French, Robert Brink, Klaus Magdorf, Santi Suryani, Jean-Laurent Casanova, Karl Bleasel, Sami Al-Hajjar, D. Sean Riminton, Joachim Roesler, Gary Y. Chew, Nicholas Simpson, Cecile King, Dan Engelhard, Cindy S. Ma, Matthew C. Cook, Stuart G. Tangye, Tyani D. Chan, Melanie Wong, Stéphanie Boisson-Dupuis, Elissa K. Deenick, Jacinta Bustamante, Peter D. Arkwright, David A. Fulcher, Saleh Al-Muhsen, Sharon Choo, Pravin Hissaria |
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| Přispěvatelé: | Faculty of Science and Engineering |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
STAT3 Transcription Factor
Time Factors Cellular differentiation Plasma Cells Immunology B-cell receptor Naive B cell Immunoglobulins Biology Immunoglobulin secretion Article FOLLICULAR-HELPER-CELLS HYPERIMMUNOGLOBULIN-E SECRETING CELLS COMMON GAMMA-CHAIN medicine Humans Immunology and Allergy Antigens Memory B cell JOBS SYNDROME B cell Common gamma chain STAPHYLOCOCCUS-AUREUS HYPER-IGE SYNDROME CUTTING EDGE PRIMARY IMMUNODEFICIENCY DISEASES Interleukins Cell Differentiation LINKED LYMPHOPROLIFERATIVE DISEASE Cell biology B-1 cell STAT1 Transcription Factor medicine.anatomical_structure Antibody Formation Immunologic Memory Signal Transduction |
| Zdroj: | The Journal of Experimental Medicine Journal of Experimental Medicine, 207(1), 155-171. ROCKEFELLER UNIV PRESS |
| ISSN: | 0022-1007 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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