title: Cutting Edge: BAFF Promotes Autoantibody Production via TACI-Dependent Activation of Transitional B Cells.
abstract: Mice overexpressing B cell activating factor of the TNF family (BAFF) develop systemic autoimmunity characterized by class-switched anti-nuclear Abs. Transmembrane activator and CAML interactor (TACI) signals are critical for BAFF-mediated autoimmunity, but the B cell developmental subsets undergoing TACI-dependent activation in settings of excess BAFF remain unclear. We report that, although surface TACI expression is usually limited to mature B cells, excess BAFF promotes the expansion of TACI-expressing transitional B cells. TACI(+) transitional cells from BAFF-transgenic mice are characterized by an activated, cycling phenotype, and the TACI(+) cell subset is specifically enriched for autoreactivity, expresses activation-induced cytidine deaminase and T-bet, and exhibits evidence of somatic hypermutation. Consistent with a potential contribution to BAFF-mediated humoral autoimmunity, TACI(+) transitional B cells from BAFF-transgenic mice spontaneously produce class-switched autoantibodies ex vivo. These combined findings highlight a novel mechanism through which BAFF promotes humoral autoimmunity via direct, TACI-dependent activation of transitional B cells.
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101;
authors.forename: Holly M
authors.identifier: 0000-0003-3250-8258
authors.initials: HM
authors.lastname: Jacobs
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101;
authors.forename: Christopher D
authors.identifier: 0000-0001-8266-975X
authors.initials: CD
authors.lastname: Thouvenel
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101;
authors.forename: Sarah
authors.identifier: 0000-0002-1960-5494
authors.initials: S
authors.lastname: Leach
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101;
authors.forename: Tanvi
authors.initials: T
authors.lastname: Arkatkar
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109; and.
authors.forename: Genita
authors.identifier: 0000-0001-8386-0150
authors.initials: G
authors.lastname: Metzler
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101;
authors.forename: Nicole E
authors.initials: NE
authors.lastname: Scharping
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109; and.
authors.forename: Nikita S
authors.initials: NS
authors.lastname: Kolhatkar
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101; Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109; and Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195 drawling@uw.edu shaun.jackson@seattlechildrens.org.
authors.forename: David J
authors.identifier: 0000-0002-0810-1776
authors.initials: DJ
authors.lastname: Rawlings
authors.affiliation: Seattle Children's Research Institute, Seattle, WA 98101; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195 drawling@uw.edu shaun.jackson@seattlechildrens.org.
authors.forename: Shaun W
authors.identifier: 0000-0002-7024-5252
authors.initials: SW
authors.lastname: Jackson
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000276:immunology; D015551:Autoimmunity; D053264:B-Cell Activating Factor / Q000235:genetics / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000276:immunology* / Q000502:physiology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D001323:Autoantibodies; D053264:B-Cell Activating Factor; C486361:Tnfrsf13b protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein