TACI regulates IgA production by APRIL in collaboration with HSPG.
Transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) is a member of the tumor necrosis factor (TNF) receptor family that serves as a receptor for B-cell activating factor of the TNF family (BAFF) and as a proliferation-inducing ligand (APRIL). Although TACI is reported to function as a positive or negative regulator for B-cell responses, its roles remain elusive. Experiments using TACI siRNA into B cells indicated that TACI positively regulated APRIL-induced IgA production in collaboration with heparan sulfate proteoglycans (HSPG). Furthermore, TACI negatively regulated BAFF-induced B-cell proliferation and production of IgA and IgG. In addition, B cells treated with heparitinase to denature HSPG showed that HSPG is essential for APRIL-induced B-cell responses such as B-cell proliferation, IgG and IgA production, induction of activation-induced cytidine deaminase (AID), and noncanonical NF-kappaB2. In contrast, phosphorylation of physiological AID kinase, protein kinase A (PKA), was dependent on TACI. Importantly, coligation of TACI and HSPG by specific antibodies, but not by TACI or HSPG ligation itself, could induce the phosphorylation of PKA and IgA production instead of APRIL. Our findings indicate that simultaneous binding of TACI and HSPG on B cells with APRIL is crucial for IgA production.
Sakurai
Daisuke
D
Department of Immunology, Dokkyo Medical University School of Medicine, Tochigi, Japan.
Hase
Hidenori
H
Kanno
Yumiko
Y
Kojima
Hidefumi
H
Okumura
Ko
K
Kobata
Tetsuji
T
D053264:B-Cell Activating Factor / Q000276:immunology / Q000494:pharmacology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004789:Enzyme Activation; D019812:Heparan Sulfate Proteoglycans / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D066298:In Vitro Techniques; D011133:Polysaccharide-Lyases; D011485:Protein Binding; D011489:Protein Denaturation; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology / Q000494:pharmacology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13 / Q000276:immunology* / Q000378:metabolism / Q000494:pharmacology
D053264:B-Cell Activating Factor; D019812:Heparan Sulfate Proteoglycans; D007070:Immunoglobulin A; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; C108467:TNFRSF13B protein, human; C114631:TNFSF13 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein; D053300:Tumor Necrosis Factor Ligand Superfamily Member 13; D017868:Cyclic AMP-Dependent Protein Kinases; D011133:Polysaccharide-Lyases; C021349:heparitinsulfate lyase