title: The TACI receptor regulates T-cell-independent marginal zone B cell responses through innate activation-induced cell death.
abstract: Activation-induced cell death (AICD) plays a critical role in immune homeostasis and tolerance. In T-cell-dependent humoral responses, AICD of B cells is initiated by Fas ligand (FasL) on T cells, stimulating the Fas receptor on B cells. In contrast, T-cell-independent B cell responses involve innate-type B lymphocytes, such as marginal zone (MZ) B cells, and little is known about the mechanisms that control AICD during innate B cell responses to Toll-like receptor (TLR) activation. Here, we show that MZ B cells undergo AICD in response to TLR4 activation in vivo. The transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI) receptor and TLR4 cooperate to upregulate expression of both FasL and Fas on MZ B cells and also to repress inhibitors of Fas-induced apoptosis signaling. These findings demonstrate an unappreciated role for TACI and its ligands in the regulation of AICD during T-cell-independent B cell responses.
authors.affiliation: Department of Immunology, Monash University, Melbourne, VIC 3004, Australia; Faculty of Medicine, University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: William A
authors.initials: WA
authors.lastname: Figgett
authors.forename: Kirsten
authors.initials: K
authors.lastname: Fairfax
authors.forename: Fabien B
authors.initials: FB
authors.lastname: Vincent
authors.forename: Mélanie A
authors.initials: MA
authors.lastname: Le Page
authors.forename: Indzi
authors.initials: I
authors.lastname: Katik
authors.forename: Devy
authors.initials: D
authors.lastname: Deliyanti
authors.forename: Pin Shie
authors.initials: PS
authors.lastname: Quah
authors.forename: Pali
authors.initials: P
authors.lastname: Verma
authors.forename: Raelene
authors.initials: R
authors.lastname: Grumont
authors.forename: Steve
authors.initials: S
authors.lastname: Gerondakis
authors.forename: Paul
authors.initials: P
authors.lastname: Hertzog
authors.forename: Lorraine A
authors.initials: LA
authors.lastname: O'Reilly
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
authors.forename: Fabienne
authors.initials: F
authors.lastname: Mackay
mesh_terms: D000818:Animals; D017209:Apoptosis; D053265:B-Cell Activation Factor Receptor / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D004789:Enzyme Activation; D053222:Fas Ligand Protein / Q000096:biosynthesis / Q000378:metabolism*; D008070:Lipopolysaccharides; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D053265:B-Cell Activation Factor Receptor; D053222:Fas Ligand Protein; C491899:Fas protein, mouse; C505658:Fasl protein, mouse; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; C486361:Tnfrsf13b protein, mouse; C486662:Tnfrsf13c protein, mouse; D051197:Toll-Like Receptor 4; D053303:Transmembrane Activator and CAML Interactor Protein; D019014:fas Receptor