Article abstract
Nature Immunology 8, 294 - 303 (2007)
Published online: 28 January 2007 | doi:10.1038/ni1434
Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI
Weifeng Xu1, Bing He1, April Chiu1, Amy Chadburn1, Meimei Shan2, Malwina Buldys1, Aihao Ding2,3, Daniel M Knowles1, Paul A Santini1 & Andrea Cerutti1,3
Abstract
Epithelial cells (ECs) transport class-switched immunoglobulin G (IgG) and IgA antibodies across mucous membranes. Whether ECs initiate class switching remains unknown. Here we found that ECs lining tonsillar crypts formed pockets populated by B cells expressing activation-induced cytidine deaminase (AID), an enzyme associated with ongoing class switching. ECs released B cell–activating AID-inducing factors after sensing microbial products through Toll-like receptors. The resulting class switching was amplified by thymic stromal lymphopoietin, an epithelial interleukin 7–like cytokine that enhanced the B cell 'licensing' function of dendritic cells, and was restrained by secretory leukocyte protease inhibitor, an epithelial homeostatic protein that inhibited AID induction in B cells. Thus, ECs may function as mucosal 'guardians' orchestrating frontline IgG and IgA class switching through a Toll-like receptor–inducible signaling program regulated by secretory leukocyte protease inhibitor.
NOTE: In the version of this article initially published online, the middle label above Figure 6c is incorrect. The correct label should be 'BAFF'. The error has been corrected for all versions of the article.
- Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
- Department of Immunology and Microbiology, Weill Medical College of Cornell University, New York, New York 10021, USA.
- Graduate Program of Immunology and Microbial Pathogenesis, Weill Medical College of Cornell University, New York, New York 10021, USA.
Correspondence to: Andrea Cerutti1,3 e-mail: acerutti@med.cornell.edu
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