Nature Immunology
1, 252 - 256 (2000)
doi:10.1038/79802
APRIL and TALL-1 and receptors BCMA and TACI: system for regulating humoral
immunityGang Yu1, Tom Boone2, John Delaney2, Nessa Hawkins3, Michael Kelley3, Meena Ramakrishnan1, Susan McCabe1, Wan-rong Qiu1, Masayo Kornuc1, Xing-Zhong Xia1, Jane Guo4, Marina Stolina4, William J. Boyle1, Ildiko Sarosi4, Hailing Hsu1, Giorgio Senaldi4
& Lars E. Theill11
Department of Inflammation, Amgen Inc., One Amgen Center
Drive, Thousand Oaks, CA 91320-1799,
USA. 2
Department of Process Science, Amgen Inc., One Amgen
Center Drive, Thousand Oaks, CA 91320-1799
, USA. 3
Department of Protein Chemistry, Amgen Inc., One Amgen
Center Drive, Thousand Oaks, CA 91320-1799
, USA. 4
Department of Pharmacology and Pathology, Amgen Inc.,
One Amgen Center Drive, Thousand Oaks, CA
91320-1799, USA.
Correspondence should be addressed to Lars E. Theill ltheill@amgen.comWe report that the tumor neurosis factor homolog APRIL (a proliferation-inducing
ligand) stimulates in vitro proliferation of primary B and T cells
and increases spleen weight due to accumulation of B cells in vivo.
APRIL functions via binding to BCMA (B cell maturation antigen) and TACI (transmembrane
activator and CAML-interactor) and competes with TALL-1 (also called BLyS
or BAFF) for receptor binding. Soluble BCMA and TACI specifically prevent
binding of APRIL and block APRIL-stimulated proliferation of primary B cells.
BCMA-Fc also inhibits production of antibodies against keyhole limpet hemocyanin
and Pneumovax in mice, indicating that APRIL and/or TALL-1 signaling via BCMA
and/or TACI are required for generation of humoral immunity. Thus, APRIL−TALL-1
and BCMA-TACI form a two ligands−two receptors pathway involved in stimulation
of B and T cell function.
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