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.
Highlights
BAFF Is a Novel Ligand of the tumor necrosis factor (TNF) Family. human BAFF (hBAFF) was identified by sequence homology as a possible novel member of the TNF ligand family while we screened public databases using an improved profile search [18]
The absence of a signal peptide suggested that BAFF was a type II membrane protein that is typical of the members of the TNF ligand family
The mouse BAFF cDNA clone isolated from a spleen library encoded a slightly longer protein (309 aa) due to an insertion between the transmembrane region and the first of several  strands which constitute the receptor binding domain in all TNF ligand members [19]
Summary
The anti-Flag M2 mAb, biotinylated anti-Flag M2 antibody, and the anti-Flag M2 antibody coupled to agarose were purchased from Sigma Chemical Co. Cell culture reagents were obtained from Life Sciences and BioWhittaker. Flag-tagged soluble human APRIL (a proliferation inducing ligand; residues K110– L250) was produced in 293 cells as described [10, 11]. FITClabeled anti-CD4, anti-CD8, and anti-CD19 antibodies were purchased from PharMingen. Goat F(abЈ) specific for the Fc5 fragment of human IgM were purchased from Jackson ImmunoResearch Laboratories. Secondary antibodies were obtained from either PharMingen or Jackson ImmunoResearch Laboratories and were used at the recommended dilutions
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