title: TACI deficiency enhances antibody avidity and clearance of an intestinal pathogen.
abstract: The transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) controls differentiation of long-lived plasma cells, and almost 10% of individuals with common variable immunodeficiency (CVID) express either the C104R or A181E variants of TACI. These variants impair TACI function, and TACI-deficient mice exhibit a CVID-like disease. However, 1%-2% of normal individuals harbor the C140R or A181E TACI variants and have no outward signs of CVID, and it is not clear why TACI deficiency in this group does not cause disease. Here, we determined that TACI-deficient mice have low baseline levels of Ig in the blood but retain the ability to mutate Ig-associated genes that encode antigen-specific antibodies. The antigen-specific antibodies in TACI-deficient mice were produced in bursts and had higher avidity than those of WT animals. Moreover, mice lacking TACI were able to clear Citrobacter rodentium, a model pathogen for severe human enteritis, more rapidly than did WT mice. These findings suggest that the high prevalence of TACI deficiency in humans might reflect enhanced host defense against enteritis, which is more severe in those with acquired or inherited immunodeficiencies.
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsuji
authors.forename: Lucas
authors.initials: L
authors.lastname: Stein
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kamada
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nuñez
authors.forename: Richard
authors.initials: R
authors.lastname: Bram
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Vallance
authors.forename: Ana E
authors.initials: AE
authors.lastname: Sousa
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Platt
authors.forename: Marilia
authors.initials: M
authors.lastname: Cascalho
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000915:Antibody Affinity; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D044082:Citrobacter rodentium / Q000276:immunology; D004751:Enteritis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D018858:Germinal Center / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000172:deficiency* / Q000235:genetics
chemical_list: D000907:Antibodies, Bacterial; C486361:Tnfrsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein