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TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation.

Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H - J. Exp. Med. (2000)

Bottom Line: Human TACI exhibits high binding affinities to both human and murine TALL-1.By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6.Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Inflammation, Amgen, Thousand Oaks, California 91320-1799, USA.

ABSTRACT
We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.

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Related in: MedlinePlus

Soluble TACI-Fc fusion protein inhibits anti-KLH and anti-Pneumovax antibody production. Mice (n = 7) were treated with 5 mg/kg TACI-Fc fusion protein or nonfused Fc protein each day for 7 d. Serum levels of anti-KLH IgG and IgM and anti-Pneumovax were measured on day 7 by ELISA.
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Figure 4: Soluble TACI-Fc fusion protein inhibits anti-KLH and anti-Pneumovax antibody production. Mice (n = 7) were treated with 5 mg/kg TACI-Fc fusion protein or nonfused Fc protein each day for 7 d. Serum levels of anti-KLH IgG and IgM and anti-Pneumovax were measured on day 7 by ELISA.

Mentions: We next examined the effect of soluble TACI protein treatment on the production of anti-KLH and anti-Pneumovax antibodies in mice. It is well known that IgG production in response to KLH requires T cell help, whereas anti-Pneumovax IgM production is T cell independent 19. Treatment with soluble TACI protein fused with Fc significantly inhibited the production of anti-KLH and anti-Pneumovax antibodies. Serum levels of anti-KLH IgG and IgM were reduced approximately four- and fivefold, respectively, in the soluble TACI-Fc treated mice compared with the control group (Fig. 4). Serum levels of anti-Pneumovax IgM were also about four times lower in the soluble TACI-Fc treated mice than in controls (Fig. 4). These findings suggest that the TALL-1–TACI interaction is involved in the generation of both T cell–dependent and independent humoral responses.


TACI is a TRAF-interacting receptor for TALL-1, a tumor necrosis factor family member involved in B cell regulation.

Xia XZ, Treanor J, Senaldi G, Khare SD, Boone T, Kelley M, Theill LE, Colombero A, Solovyev I, Lee F, McCabe S, Elliott R, Miner K, Hawkins N, Guo J, Stolina M, Yu G, Wang J, Delaney J, Meng SY, Boyle WJ, Hsu H - J. Exp. Med. (2000)

Soluble TACI-Fc fusion protein inhibits anti-KLH and anti-Pneumovax antibody production. Mice (n = 7) were treated with 5 mg/kg TACI-Fc fusion protein or nonfused Fc protein each day for 7 d. Serum levels of anti-KLH IgG and IgM and anti-Pneumovax were measured on day 7 by ELISA.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1887716&req=5

Figure 4: Soluble TACI-Fc fusion protein inhibits anti-KLH and anti-Pneumovax antibody production. Mice (n = 7) were treated with 5 mg/kg TACI-Fc fusion protein or nonfused Fc protein each day for 7 d. Serum levels of anti-KLH IgG and IgM and anti-Pneumovax were measured on day 7 by ELISA.
Mentions: We next examined the effect of soluble TACI protein treatment on the production of anti-KLH and anti-Pneumovax antibodies in mice. It is well known that IgG production in response to KLH requires T cell help, whereas anti-Pneumovax IgM production is T cell independent 19. Treatment with soluble TACI protein fused with Fc significantly inhibited the production of anti-KLH and anti-Pneumovax antibodies. Serum levels of anti-KLH IgG and IgM were reduced approximately four- and fivefold, respectively, in the soluble TACI-Fc treated mice compared with the control group (Fig. 4). Serum levels of anti-Pneumovax IgM were also about four times lower in the soluble TACI-Fc treated mice than in controls (Fig. 4). These findings suggest that the TALL-1–TACI interaction is involved in the generation of both T cell–dependent and independent humoral responses.

Bottom Line: Human TACI exhibits high binding affinities to both human and murine TALL-1.By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6.Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation.

View Article: PubMed Central - PubMed

Affiliation: Department of Inflammation, Amgen, Thousand Oaks, California 91320-1799, USA.

ABSTRACT
We and others recently reported tumor necrosis factor (TNF) and apoptosis ligand-related leukocyte-expressed ligand 1 (TALL-1) as a novel member of the TNF ligand family that is functionally involved in B cell proliferation. Transgenic mice overexpressing TALL-1 have severe B cell hyperplasia and lupus-like autoimmune disease. Here, we describe expression cloning of a cell surface receptor for TALL-1 from a human Burkitt's lymphoma RAJI cell library. The cloned receptor is identical to the previously reported TNF receptor (TNFR) homologue transmembrane activator and calcium modulator and cyclophilin ligand (CAML) interactor (TACI). Murine TACI was subsequently isolated from the mouse B lymphoma A20 cells. Human and murine TACI share 54% identity overall. Human TACI exhibits high binding affinities to both human and murine TALL-1. Soluble TACI extracellular domain protein specifically blocks TALL-1-mediated B cell proliferation without affecting CD40- or lipopolysaccharide-mediated B cell proliferation in vitro. In addition, when injected into mice, soluble TACI inhibits antibody production to both T cell-dependent and -independent antigens. By yeast two-hybrid screening of a B cell library with TACI intracellular domain, we identified that, like many other TNFR family members, TACI intracellular domain interacts with TNFR-associated factor (TRAF)2, 5, and 6. Correspondingly, TACI activation in a B cell line results in nuclear factor kappaB and c-Jun NH(2)-terminal kinase activation. The identification and characterization of the receptor for TALL-1 provides useful information for the development of a treatment for B cell-mediated autoimmune diseases such as systemic lupus erythematosus.

Show MeSH
Related in: MedlinePlus