BLyS and APRIL form biologically active heterotrimers that are expressed in patients with systemic immune-based rheumatic diseases.
BLyS and APRIL are two members of the TNF superfamily that are secreted by activated myeloid cells and have costimulatory activity on B cells. BLyS and APRIL share two receptors, TACI and BCMA, whereas a third receptor, BAFF-R, specifically binds BLyS. Both BLyS and APRIL have been described as homotrimeric molecules, a feature common to members of the TNF superfamily. In this study, we show that APRIL and BLyS can form active heterotrimeric molecules when coexpressed and that circulating heterotrimers are present in serum samples from patients with systemic immune-based rheumatic diseases. These findings raise the possibility that active BLyS/APRIL heterotrimers may play a role in rheumatic and other autoimmune diseases and that other members of the TNF ligand superfamily may also form active soluble heterotrimers.
Roschke
Viktor
V
Department of Antibody Development, Human Genome Sciences, 9410 Key West Avenue, Rockville, MD 20850, USA.
Sosnovtseva
Svetlana
S
Ward
Christopher D
CD
Hong
June S
JS
Smith
Rodger
R
Albert
Vivian
V
Stohl
William
W
Baker
Kevin P
KP
Ullrich
Stephen
S
Nardelli
Bernardetta
B
Hilbert
David M
DM
Migone
Thi-Sau
TS
D000818:Animals; D015535:Arthritis, Psoriatic / Q000097:blood / Q000276:immunology; D016918:Arthritis, Reactive / Q000097:blood / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017285:Polymyositis / Q000097:blood / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis* / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D012216:Rheumatic Diseases / Q000097:blood / Q000276:immunology*; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology*
D053265:B-Cell Activation Factor Receptor; C120197:BLyS receptor; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; C435926:TNFRSF13C protein, human; C114631:TNFSF13 protein, human; C486662:Tnfrsf13c protein, mouse; C491959:Tnfsf13 protein, mouse; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D014409:Tumor Necrosis Factor-alpha