Epithelial cells trigger frontline immunoglobulin class switching through a pathway regulated by the inhibitor SLPI.
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.
Xu
Weifeng
W
Department of Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York 10021, USA.
He
Bing
B
Chiu
April
A
Chadburn
Amy
A
Shan
Meimei
M
Buldys
Malwina
M
Ding
Aihao
A
Knowles
Daniel M
DM
Santini
Paul A
PA
Cerutti
Andrea
A
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
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