BAFF, a Novel Ligand of the Tumor Necrosis Factor Family, Stimulates B Cell Growth

Abstract

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M–stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center–like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.

The Abnormal High Expression of B Cell Activating Factor Belonging to TNF Superfamily (BAFF) and Its Potential Role in Kidney Transplant Recipients

“…And the BAFF on T cells may bind to BCMA on B cells providing more survival signal to increase basal survival of B cells, and resulting in more production of antibodies (24). Is increase of Nardelli et al reported that sBAFF is produced by enzymatic processing of the membrane-bound protein by conducting experiments with cells transfected with a mutant BAFF cDNA (25), as suggested in Schneider's previous report (26). Because the BAFF sequence does not contain a predicted signal peptide, a possible mechanism for the release of BAFF from the cells is the proteolytic cleavage of the membrane-bound protein.…”

BAFF and the plasticity of peripheral B cell tolerance

“…Initial descriptions of BAFF revealed profound positive effects on mature B cells both in vivo and in vitro [18,19]. The subsequent discovery of BAFFr, a B-lineage restricted receptor whose sole natural ligand is BAFF, showed that BAFF-BAFFr interactions were crucial to maintaining normal peripheral B cell numbers [20,21].…”

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.…”

“…[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.…”