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

Abstract

TALL-1͞Blys͞BAFF 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 lupuslike changes in transgenic mice expressing TALL-1 under the control of a ␤-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 cellassociated autoimmune diseases.TNF ligand family ͉ B cell stimulation

351 Differential Requirement of MALT1 for BAFF-induced Outcomes in B Cell Subsets

“…Our results suggest that MALT1 is a critical intermediate phenotype does not occur in the absence of MALT1. In addition, the expansion of the B1 B cell compartment in the peritoneum has also been reported in BAFF-Tg animals, albeit to varying degrees in diff erent studies Khare et al, 2000 ;Gavin et al, 2005 ). In our hands, we see reproducible increases in the B1 B cell population in the presence of the BAFF transgene that are ablated in the context of either MALT1 or Bcl10 defi ciency.…”

“…BAFF-induced transitional B cell survival is required for the development of mature B cell subsets, including CD21 low CD23 high follicular (FO) B cells as well as CD21 high CD23 low marginal zone (MZ) B cells ( Batten et al, 2000 ). Mice that overexpress BAFF (BAFF-Tg) exhibit an expanded MZ B cell compartment, hyper-Ig production, and spontaneous germinal center (GC) formation concomitant with autoimmune symptoms Khare et al, 2000 ).…”

Construction and expression of a new fusion protein, thymosin ?1?cBLyS, E. coli

“…TMa1-cBLyS alone could not induce significant proliferation of murine B cells when compared to cells cultured with media alone (Figure 4), just like BLyS (Khare et al 2000). However, when used in a costimulation assay with anti-IgM, TMa1-BLyS was able to stimulate the proliferation of B cells.…”

Expression of BAFF-R (BR3) in normal and neoplastic lymphoid tissues characterized with a newly developed monoclonal antibody

“…BAFF is a trimeric membranebound or soluble factor and is expressed by monocytes, macrophages, neutrophils and dendritic cells. Whereas BAFF-deficient mice lack mature B-cells, BAFF-transgenic mice, characterized by overexpression of BAFF, have increased the number of B-cells and develop autoimmunity [3,4,9,12]. In particular, transitional type 2 (T2) B-cells and marginal zone B-cells are expanded in BAFF-transgenic mice.…”