APRIL and TALL-I and receptors BCMA and TACI: system for regulating humoral immunity.
We 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-I (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-I signaling via BCMA and/or TACI are required for generation of humoral immunity. Thus, APRIL-TALL-I and BCMA-TACI form a two ligands-two receptors pathway involved in stimulation of B and T cell function.
Yu
G
G
Department of Inflammation, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799, USA.
Boone
T
T
Delaney
J
J
Hawkins
N
N
Kelley
M
M
Ramakrishnan
M
M
McCabe
S
S
Qiu
W R
WR
Kornuc
M
M
Xia
X Z
XZ
Guo
J
J
Stolina
M
M
Boyle
W J
WJ
Sarosi
I
I
Hsu
H
H
Senaldi
G
G
Theill
L E
LE
D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000941:Antigens / Q000276:immunology; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001667:Binding, Competitive; D002452:Cell Count; D005260:Female; D006433:Hemocyanins / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D009929:Organ Size / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013154:Spleen / Q000033:anatomy & histology / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D053303:Transmembrane Activator and CAML Interactor Protein; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism
C490341:ANP32B protein, human; D000941:Antigens; D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; D008565:Membrane Proteins; D009479:Neuropeptides; D009687:Nuclear Proteins; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C108467:TNFRSF13B protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; C486361:Tnfrsf13b protein, mouse; C490176:Tnfrsf17 protein, mouse; C505720:Tnfsf13b protein, mouse; D053303:Transmembrane Activator and CAML Interactor Protein; D014409:Tumor Necrosis Factor-alpha; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin