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BAFF (BLyS / TALL1)

BAFF /APRIL functions

BAFF (B cell activation factor of the TNF family, also known as BLyS or TALL1) is a cytokine expressed predominantly by cells of the immune system such as neutrophils, monocytes, macrophages, dendritic cells, follicular dendritic cells, activated T cells and some malignant B cells. BAFF is a master regulator of peripheral B cell survival, and also acts in processes such as immunoglobulin isotype switch and B cell co-stimulation. Beside its major role in B cell biology, BAFF co-stimulates activated T cells. BAFF is found either at the cell membrane as a type II transmembrane protein or it is released in a soluble form[1].

APRIL (A Proliferation-inducing ligand; TRDL-1) is a secreted protein related to BAFF and shares some of the BAFF receptors. APRIL is expressed in monocytes, dendritic cells and T cells. In contrast to BAFF, APRIL is also expressed in several tumor tissues or cell lines, such as colon carcinoma[2].

BAFF and APRIL both bind to TACI (transmembrane activator and CAML-interactor) and BCMA (B cell maturation antigen). BAFF, but not APRIL also signals through BAFF Receptor (BAFF-R, BR3). All three receptors are expressed during B cell differentiation, although activated T cells also express BAFF-R. A new third “receptor” for APRIL has been reported: the glycosaminoglycans side chains of proteoglycans are an APRIL-specific binding partner[3, 4] (Figure 1).

BAFF and diseases

Deregulated expression of BAFF leads to autoimmune disorders in mice. In the human, elevated levels of soluble BAFF have been detected in the serum of patients with various autoimmune diseases, such as rheumatoid arthritis (RA), Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) and in patients with tumors, such as multiple myeloma (MM) non-Hodgkin lymphoma (NHL), including B-cell chronic lymphocytic leukemia (B-CLL)[5]. APRIL promotes tumor formation, as APRIL transgenic mice develop lymph node hyperplasia that are reminiscent of human B-CLL (the most prevalent leukemia in Western countries)[6]. Mutations in the BAFF-R and TACI are associated with Common Variable Immunodeficiency (CVID) in humans[7, 8].

Figure 1: Functions of BAFF and APRIL and its receptors in the immune system. BAFF and APRIL interactions with their receptors and functional outcomes of BAFF and /or APRIL signaling are shown.

BAFF, Soluble (mouse) Detection Set (APO-54N-013)

Summary of features

	For the quantitative determination of soluble mouse BAFF from biological fluids (serum and cell culture supernatant)
	Monoclonal antibodies-based sandwich ELISA
	Detection limit: 0.3 ng / ml
	Range: 0-20 ng / ml
	Specificity : Detects only mouse BAFF
	Format: contains sufficient materials to run ELISAs on 4 x 96-well plates

Principle of the Kit

This assay is a sandwich Enzyme Linked-Immuno-Sorbent Assay (ELISA) developed for the direct measurement of mouse BAFF (mBAFF) in serum and cell culture supernatants. A monoclonal antibody specific for mBAFF is coated onto the wells of the supplied microtiter strips. Samples and concentration standards of mBAFF are pipetted into the wells for binding to the coated antibody. After extensive washing to remove unbound compounds, mBAFF is recognized by the addition of a biotinylated monoclonal antibody specific for mBAFF. After removal of excess biotinylated antibody, streptavidine-peroxidase is added. Following a final washing, peroxidase activity is quantified using the substrate 3,3’,5,5’-tetramethylbenzidine (TMB). The intensity of the color reaction is measured at 450 nm after acidification and is directly proportional to the concentration of mBAFF in the samples.

Figure 2: Linearity of the STD curve.

LITERATURE OVERVIEW:

[1]            Schneider, P. (2005). The role of APRIL and BAFF in lymphocyte activation. Curr Opin Immunol 17, 282-289.

[2]            Rennert, P., Schneider, P., Cachero, T.G., Thompson, J., Trabach, L., Hertig, S., Holler, N., Qian, F., Mullen, C., Strauch, K., Browning, J.L., Ambrose, C., and Tschopp, J. (2000). A soluble form of B cell maturation antigen, a receptor for the tumor necrosis factor family member APRIL, inhibits tumor cell growth. J Exp Med 192, 1677-1684.

[3]            Ingold, K., Zumsteg, A., Tardivel, A., Huard, B., Steiner, Q.G., Cachero, T.G., Qiang, F., Gorelik, L., Kalled, S.L., Acha-Orbea, H., Rennert, P.D., Tschopp, J., and Schneider, P. (2005). Identification of proteoglycans as the APRIL-specific binding partners. J Exp Med 201, 1375-1383.

[4]            Hendriks, J., Planelles, L., de Jong-Odding, J., Hardenberg, G., Pals, S.T., Hahne, M., Spaargaren, M., and Medema, J.P. (2005). Heparan sulfate proteoglycan binding promotes APRIL-induced tumor cell proliferation. Cell Death Differ 12, 637-648.

[5]            Mackay, F., and Tangye, S.G. (2004). The role of the BAFF/APRIL system in B cell homeostasis and lymphoid cancers. Curr Opin Pharmacol 4, 347-354.

[6]            Planelles, L., Carvalho-Pinto, C.E., Hardenberg, G., Smaniotto, S., Savino, W., Gomez-Caro, R., Alvarez-Mon, M., de Jong, J., Eldering, E., Martinez, A.C., Medema, J.P., and Hahne, M. (2004). APRIL promotes B-1 cell-associated neoplasm. Cancer Cell 6, 399-408.

[7]            Salzer, U., Chapel, H.M., Webster, A.D., Pan-Hammarstrom, Q., Schmitt-Graeff, A., Schlesier, M., Peter, H.H., Rockstroh, J.K., Schneider, P., Schaffer, A.A., Hammarstrom, L., and Grimbacher, B. (2005). Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet 37, 820-828.

[8]            Losi, C.G., Silini, A., Fiorini, C., Soresina, A., Meini, A., Ferrari, S., Notarangelo, L.D., Lougaris, V., and Plebani, A. (2005). Mutational Analysis of Human BAFF Receptor TNFRSF13C (BAFF-R) in Patients with Common Variable Immunodeficiency. J Clin Immunol 25, 496-502.