Severe B cell hyperplasia and autoimmune disease in TALL-1 transgenic mice

TLDR

TALL‑1/Blys/BAFF, a TNF ligand, promotes B cell proliferation. The study examined B cell hyperplasia and lupus‑like autoimmunity in mice overexpressing TALL‑1 driven by a beta‑actin promoter. TALL‑1 transgenic mice displayed marked splenomegaly, lymphadenopathy, and Peyer's patch enlargement driven by increased B220+ cells, hypergammaglobulinemia across all Ig classes, and lupus‑like autoimmunity with anti‑nuclear antibodies and renal immune complex deposition, indicating that sustained B‑cell activation by TALL‑1 promotes autoimmune disease.

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.