Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 207, Issue 1, Pages 155-171Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20091706
Keywords
-
Categories
Funding
- Australian National Health and Medical Research Council
- Fondation BNP Paribas
- Fondation Schlumberger
- Institut Universitaire de France
- March of Dimes
- Dana Foundation
- Agence Nationale pour la Recherche
- Howard Hughes Medical Institute
Ask authors/readers for more resources
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available