Article abstract
Nature Immunology 8, 522 - 531 (2007)
Published online: 1 April 2007 | Corrected online: 30 May 2007 | doi:10.1038/ni1452
Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development
Alexander Astrakhan1, Miyuki Omori2,7, Thuc Nguyen3,7, Shirly Becker-Herman4,7, Masanori Iseki2,7, Theingi Aye2, Kelly Hudkins5, James Dooley6, Andrew Farr1,6, Charles E Alpers5, Steven F Ziegler1,2 & David J Rawlings1,4
Abstract
The cytokine thymic stromal lymphopoietin (TSLP) drives immature B cell development in vitro and may regulate T helper type 2 responses. Here we analyzed the involvement of TSLP in B cell development in vivo with a doxycycline-inducible, keratin 5–driven transgene encoding TSLP (K5-TSLP). K5-TSLP-transgenic mice given doxycycline showed an influx of immature B cells into the periphery, with population expansion of follicular mature B cells, near-complete loss of marginal zone and marginal zone precursor B cells, and 'preferential' population expansion of peritoneal B-1b B cells. These changes promoted cryoglobulin production and immune complex–mediated renal disease. Identical events occurred in mice without T cells, in alternative TSLP-transgenic models and in K5-TSLP-transgenic mice with undetectable systemic TSLP. These observations suggest that signals mediating localized TSLP expression may modulate systemic B cell development and promote humoral autoimmunity.
- Department of Immunology, University of Washington School of Medicine Seattle, Washington 98195, USA.
- Benaroya Research Institute, Seattle, Washington 98195, USA.
- Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195, USA.
- Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington 98195, USA.
- Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195, USA.
- Department of Biological Structure, University of Washington School of Medicine, Seattle, Washington 98195, USA.
- These authors contributed equally to this work.
Correspondence to: David J Rawlings1,4 e-mail: drawling@u.washington.edu
Correspondence to: Steven F Ziegler1,2 e-mail: sziegler@benaroyaresearch.org
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