Journal
NATURE IMMUNOLOGY
Volume 8, Issue 5, Pages 522-531Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ni1452
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Funding
- NIAID NIH HHS [R01 AI44259, R01 AI068731] Funding Source: Medline
- NICHD NIH HHS [R01 HD37091] Funding Source: Medline
- NIDDK NIH HHS [P30 DK47754, R01 DK66802, R01 DK072295] Funding Source: Medline
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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.
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