Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development.
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.
Astrakhan
Alexander
A
Department of Immunology, University of Washington School of Medicine Seattle, Washington 98195, USA.
Omori
Miyuki
M
Nguyen
Thuc
T
Becker-Herman
Shirly
S
Iseki
Masanori
M
Aye
Theingi
T
Hudkins
Kelly
K
Dooley
James
J
Farr
Andrew
A
Alpers
Charles E
CE
Ziegler
Steven F
SF
Rawlings
David J
DJ
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
D016207:Cytokines; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse