Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice.
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.
Khare
S D
SD
Department, Pharmacology, Amgen, 1 Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
Sarosi
I
I
Xia
X Z
XZ
McCabe
S
S
Miner
K
K
Solovyev
I
I
Hawkins
N
N
Kelley
M
M
Chang
D
D
Van
G
G
Ross
L
L
Delaney
J
J
Wang
L
L
Lacey
D
D
Boyle
W J
WJ
Hsu
H
H
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*
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