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Merck
  • Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development.

Local increase in thymic stromal lymphopoietin induces systemic alterations in B cell development.

Nature immunology (2007-04-03)
Alexander Astrakhan, Miyuki Omori, Thuc Nguyen, Shirly Becker-Herman, Masanori Iseki, Theingi Aye, Kelly Hudkins, James Dooley, Andrew Farr, Charles E Alpers, Steven F Ziegler, David J Rawlings
摘要

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.