Document Detail


Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI.
MedLine Citation:
PMID:  17259987     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Weifeng Xu; Bing He; April Chiu; Amy Chadburn; Meimei Shan; Malwina Buldys; Aihao Ding; Daniel M Knowles; Paul A Santini; Andrea Cerutti
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2007-01-28
Journal Detail:
Title:  Nature immunology     Volume:  8     ISSN:  1529-2908     ISO Abbreviation:  Nat. Immunol.     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-02-16     Completed Date:  2007-05-01     Revised Date:  2013-05-17    
Medline Journal Info:
Nlm Unique ID:  100941354     Medline TA:  Nat Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  294-303     Citation Subset:  IM    
Affiliation:
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
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MeSH Terms
Descriptor/Qualifier:
B-Cell Activating Factor / immunology,  metabolism
B-Lymphocytes / immunology*,  metabolism
Cells, Cultured
Cytokines / immunology,  metabolism
Electrophoretic Mobility Shift Assay
Enzyme-Linked Immunosorbent Assay
Epithelial Cells / immunology*,  metabolism
Flow Cytometry
Humans
Immunity, Mucosal
Immunoblotting
Immunoglobulin A / immunology
Immunoglobulin Class Switching*
Immunoglobulin G / immunology
Immunohistochemistry
In Situ Hybridization
Interleukin-10 / immunology,  metabolism
Palatine Tonsil / cytology,  immunology
RNA, Viral / immunology
Reverse Transcriptase Polymerase Chain Reaction
Secretory Leukocyte Peptidase Inhibitor / immunology*,  metabolism
Signal Transduction / immunology*
Toll-Like Receptors / immunology,  metabolism
Grant Support
ID/Acronym/Agency:
AI057653/AI/NIAID NIH HHS; R01 AI057653/AI/NIAID NIH HHS; R01 AI074378/AI/NIAID NIH HHS; R21 AI057130/AI/NIAID NIH HHS; T32 AI07621/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/B-Cell Activating Factor; 0/Cytokines; 0/Immunoglobulin A; 0/Immunoglobulin G; 0/RNA, Viral; 0/SLPI protein, human; 0/Secretory Leukocyte Peptidase Inhibitor; 0/TNFSF13B protein, human; 0/Toll-Like Receptors; 0/thymic stromal lymphopoietin; 130068-27-8/Interleukin-10
Comments/Corrections
Comment In:
Nat Immunol. 2007 Mar;8(3):230-2   [PMID:  17304230 ]

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