Mice Transgenic for Baff Develop Lymphocytic Disorders along with Autoimmune Manifestations

Abstract

The cause of many autoimmune and inflammatory diseases is unresolved, although dysregulated production of tumor necrosis factor (TNF) family members appears to be important in many cases. BAFF, a new member of the TNF family, binds to B cells and costimulates their growth in vitro. Mice transgenic for BAFF have vastly increased numbers of mature B and effector T cells, and develop autoimmune-like manifestations such as the presence of high levels of rheumatoid factors, circulating immune complexes, anti–DNA autoantibodies, and immunoglobulin deposition in the kidneys. This phenotype is reminiscent of certain human autoimmune disorders and suggests that dysregulation of BAFF expression may be a critical element in the chain of events leading to autoimmunity.

A Pilot Study of the Therapeutic Efficacy and Mechanism of Artesunate in the MRL/lpr Murine Model of Systemic Lupus Erythematosus

“…Studies have shown that the serum BAFF levels were increased in the MRL/lpr mice (20,21). Using the blocking agent, TACI-Ig or BCMA-Ig could delay the process of SLE by inhibiting the activation of B cells (22).…”

“…The change of autoantibody and pro-inflammation cytokine levels in serum and urine, the monocyte chemotactic protein-1 (MCP-1) expression in kidney and the B cell activating factor (BAFF) (11)(12)(13)(14)(15) expression in spleen, all of which may play a role in the development of lupus nephritis, was also determined to explore the mechanism of action of artesunate.…”

Analysis on the association of human BLYS (BAFF, TNFSF13B) polymorphisms with systemic lupus erythematosus and rheumatoid arthritis

“…[1][2][3][4][5] BLyS is a potent B cell co-stimulator, and promotes B cell differentiation, proliferation and survival. 1,2,[6][7][8][9][10] In BLyS deficient mice, the number of B cells, serum IgG and IgM levels were decreased, and B cell development was blocked at the transitional T1 stage. 11 BLyS and a proliferation-inducing ligand (APRIL) bind to B cell maturation antigen (BCMA) and transmembrane activator and CAML-interactor (TACI), 4,12,13 which belong to the tumor necrosis factor receptor superfamily and are mainly expressed in B cells.…”

“…Transgenic mice overexpressing BLyS develop symptoms characteristic of systemic lupus erythematosus (SLE). 4,6,7 Circulating BLyS is elevated in SLE model mice, NZB/W F1 and MRL-lpr/ lpr. 4 In addition, TACI-Ig treatment inhibits development of proteinurea in NZB/W F1 mice, and the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis (RA).…”

BAFF synthesis by rheumatoid synoviocytes is positively controlled by α5β1 integrin stimulation and is negatively regulated by tumor necrosis factor α and toll‐like receptor ligands

“…suggested a critical role of BAFF in autoimmune diseases (5)(6)(7). Elevated levels of BAFF have been detected in serum and synovial fluid samples from patients with rheumatoid arthritis (RA), and it was recently demonstrated that overproduction of BAFF by dendritic cells and macrophages may play a crucial role in the pathogenesis of experimental arthritis (8,9).…”