title: Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Xu
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.forename: April
authors.initials: A
authors.lastname: Chiu
authors.forename: Amy
authors.initials: A
authors.lastname: Chadburn
authors.forename: Meimei
authors.initials: M
authors.lastname: Shan
authors.forename: Malwina
authors.initials: M
authors.lastname: Buldys
authors.forename: Aihao
authors.initials: A
authors.lastname: Ding
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Knowles
authors.forename: Paul A
authors.initials: PA
authors.lastname: Santini
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
mesh_terms: D053264:B-Cell Activating Factor / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D018928:Immunity, Mucosal; D015151:Immunoblotting; D007070:Immunoglobulin A / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000276:immunology; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D012367:RNA, Viral / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000276:immunology* / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D053264:B-Cell Activating Factor; D016207:Cytokines; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012367:RNA, Viral; C506814:SLPI protein, human; D053481:Secretory Leukocyte Peptidase Inhibitor; C505719:TNFSF13B protein, human; D051193:Toll-Like Receptors; D016753:Interleukin-10; D000094632:Thymic Stromal Lymphopoietin