title: Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development.
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.
authors.affiliation: Department of Immunology, University of Washington School of Medicine Seattle, Washington 98195, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Astrakhan
authors.forename: Miyuki
authors.initials: M
authors.lastname: Omori
authors.forename: Thuc
authors.initials: T
authors.lastname: Nguyen
authors.forename: Shirly
authors.initials: S
authors.lastname: Becker-Herman
authors.forename: Masanori
authors.initials: M
authors.lastname: Iseki
authors.forename: Theingi
authors.initials: T
authors.lastname: Aye
authors.forename: Kelly
authors.initials: K
authors.lastname: Hudkins
authors.forename: James
authors.initials: J
authors.lastname: Dooley
authors.forename: Andrew
authors.initials: A
authors.lastname: Farr
authors.forename: Charles E
authors.initials: CE
authors.lastname: Alpers
authors.forename: Steven F
authors.initials: SF
authors.lastname: Ziegler
authors.forename: David J
authors.initials: DJ
authors.lastname: Rawlings
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D001402:B-Lymphocytes / Q000502:physiology*; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse