title: Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice.
abstract: TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TNF) ligand superfamily that is functionally involved in B cell proliferation. Here, we describe B cell hyperplasia and autoimmune lupus-like changes in transgenic mice expressing TALL-1 under the control of a beta-actin promoter. The TALL-1 transgenic mice showed severe enlargement of spleen, lymph nodes, and Peyer's patches because of an increased number of B220+ cells. The transgenic mice also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE. In addition, a phenotype similar to autoimmune lupus-like disease was also seen in TALL-1 transgenic mice, characterized by the presence of autoantibodies to nuclear antigens and immune complex deposits in the kidney. Prolonged survival and hyperactivity of transgenic B cells may contribute to the autoimmune lupus-like phenotype in these animals. Our studies further confirm TALL-1 as a stimulator of B cells that affect Ig production. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmune diseases.
authors.affiliation: Department, Pharmacology, Amgen, 1 Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Khare
authors.forename: I
authors.initials: I
authors.lastname: Sarosi
authors.forename: X Z
authors.initials: XZ
authors.lastname: Xia
authors.forename: S
authors.initials: S
authors.lastname: McCabe
authors.forename: K
authors.initials: K
authors.lastname: Miner
authors.forename: I
authors.initials: I
authors.lastname: Solovyev
authors.forename: N
authors.initials: N
authors.lastname: Hawkins
authors.forename: M
authors.initials: M
authors.lastname: Kelley
authors.forename: D
authors.initials: D
authors.lastname: Chang
authors.forename: G
authors.initials: G
authors.lastname: Van
authors.forename: L
authors.initials: L
authors.lastname: Ross
authors.forename: J
authors.initials: J
authors.lastname: Delaney
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: D
authors.initials: D
authors.lastname: Lacey
authors.forename: W J
authors.initials: WJ
authors.lastname: Boyle
authors.forename: H
authors.initials: H
authors.lastname: Hsu
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000032:analysis; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology*; D053264:B-Cell Activating Factor; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D001483:Base Sequence; D017931:DNA Primers; D006942:Hypergammaglobulinemia / Q000276:immunology; D007668:Kidney / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D053264:B-Cell Activating Factor; D017931:DNA Primers; D008565:Membrane Proteins; C505720:Tnfsf13b protein, mouse; D014409:Tumor Necrosis Factor-alpha