The human B cell activating factor (BAFF) and APRIL(a proliferation inducing ligand) are both type II molecules belonging to the TNF superfamily. They are expressed by non-B cells, and are down regulated by mitogenic stimulation(2). BAFF and APRIL bind to at least two receptors: TACI (transmembrane activator and CAML-interactor) and BCMA (B cell maturation antigen), both of which are restricted to B cells(3,4). Ligation of these receptors with recombinant BAFF dramatically increases IgM production by peripheral blood B cells(1). A third receptor for BAFF (BAFF-R) has been described(5). BAFF and BAFFR knockout mice have a reduced numbers of mature B cells in the periphery, however TACI and BCMA knockouts do not share this phenotype, suggesting that BAFF-R may the primary receptor for BAFF in mice(8,9,10). Cell surface BAFF can be proteolytically cleaved to form a soluble trimeric molecule(2). Levels of soluble BAFF correspond with levels of autoantibodies in Sjogren’s Syndrome(11). Recombinant human BAFFR-muIg binds to recombinant BAFF-muCD8 and can inhibit binding of this molecule to receptors on Raji cells.
Molecular Structure: A soluble molecule consisting of the extracellular (60aa) domain of human BAFFR fused to the murine IgG2a Fc (232 aa). Predicted non glycosylated monomeric weight: 33.5 kd.
Murine CD8alpha leader: kpqapelrgs
linker: gs
BAFFR (EC): rgprslrgrdapaptpcvpaecfdllvrhcvacgllrtprpkpagassppprtal
linker: gt
Murine IgG2a Fc + hinge: eprgptikpcppckcpapnllggpsvfifppkikdvlmislspivtcvvvdvseddpdvqiswfvnnvevhtaqtqthredynstlrvvsalpiqhqdwmsgkefkckvnnkdlpapiertiskpkgsvrapqvyvlpppeeemtkkqvtltcmvtdfmpediyvewtnngktelnykntepvldsdgsyfmysklrvekknwvernsyscsvvheglhnhhttksfsrtpgk
Transfectant Cell Line: CHO
Functional Application: BAFFR-muIg binds to recombinant BAFF-muCD8 and can inhibit this molecule’s abiltiy to bind to receptors on Raji cells.
References:
1) Schneider P., J. Tschopp, et al. J. Exp. Med. 1999, 189(11):1747-1756.
2) Shu, H.B., H. Johnson, W.H. Hui. J Leukoc Biol 1999, 65:680-683.
3) Marsters, S.A., A. Ashkenazi, et al. 2000, Curr Biol 10:785-788.
4) Xia, X., H. Hsu, et al. 2000, J Exp Med, 192(1): 137-143.
5) Thompson J.S., C. Ambrose, et al. Science 2001, 293: 2108-2111.
6)Roschke,V, T.S. Migone, et al. J Immunol . 2002, 169: 4314-4321.
7) MacLennan, C.M., C.G. Vinuesa, 2002, Immunity 17:235-238.
8) B. Schiemann, et al, (2001) Science 293: 2111-2114.
9) S.M. Harless,et al, (2001) Curr Biol 11: 1988-1989.
10) Mol Cell Biol (2001) 21: 4067-4074.
11) X. Mariette, et al, (2003) Ann Rhem Dis 62: 168-171.
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