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

TALL-1/Blys/BAFF is a member of the tumor necrosis factor (TMF) ligand supe rfamily that is functionally involved in B cell proliferation. Here, we des cribe B cell hyperplasia and autoimmune lupuslike changes in transgenic mic e 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 mi ce also had hypergammaglobulinemia contributed by elevations of serum IgM, IgG, IgA, and IgE, In addition, a phenotype similar to autoimmune lupus-lik e disease was also seen in TALL-1 transgenic mice, characterized by the pre sence 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 stu dies further confirm TALL-1 as a stimulator of B cells that affect Ig produ ction. Thus, TALL-1 may be a primary mediator in B cell-associated autoimmu ne diseases.