title: Decoy receptor 3 suppresses TLR2-mediated B cell activation by targeting NF-κB.
abstract: Decoy receptor 3 (DcR3) is a soluble protein in the TNFR superfamily. Its known ligands include Fas ligand, homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes, TNF-like molecule 1A, and heparan sulfate proteoglycans. DcR3 has been reported to modulate the functions of T cells, dendritic cells, and macrophages; however, its role in regulating B cell activation is largely unknown. In this study, we found that the DcR3.Fc fusion protein bound to human and mouse B cells and suppressed the activation of B cells. DcR3.Fc attenuated Staphylococcus aureus, IgM-, Pam(3)CSK(4)-, and LPS-mediated B cell proliferation but did not affect cytokine-induced B cell growth. In the presence of these mitogens, DcR3.Fc did not induce B cell apoptosis, suggesting that DcR3 may inhibit the signal(s) important for B cell activation. Because the combination of Fas.Fc, LT-βR.Fc (homologous to lymphotoxin, showing inducible expression, and competing with HSV glycoprotein D for herpes virus entry mediator, a receptor expressed by T lymphocytes receptor), and DR3.Fc (TNF-like molecule 1A receptor) did not suppress B cell proliferation and because the biological effect of DcR3.Fc on B cells was not blocked by heparin, we hypothesize that a novel ligand(s) of DcR3 mediates its inhibitory activity on B cells. Moreover, we found that TLR2-stimulated NF-κB p65 activation and NF-κB-driven luciferase activity were attenuated by DcR3.Fc. The TLR2-induced cytokine production by B cells was consistently reduced by DcR3. These results imply that DcR3 may regulate B cell activation by suppressing the activation of NF-κB.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei 11221, Taiwan.
authors.forename: Zi-Ming
authors.initials: ZM
authors.lastname: Huang
authors.forename: Jhi-Kai
authors.initials: JK
authors.lastname: Kang
authors.forename: Chih-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Tz-Hau
authors.initials: TH
authors.lastname: Tseng
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Chang
authors.forename: Yung-Chi
authors.initials: YC
authors.lastname: Chang
authors.forename: Shyh-Kuan
authors.initials: SK
authors.lastname: Tai
authors.forename: Shie-Liang
authors.initials: SL
authors.lastname: Hsieh
authors.forename: Chuen-Miin
authors.initials: CM
authors.lastname: Leu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D053323:Receptors, Tumor Necrosis Factor, Member 6b / Q000276:immunology* / Q000378:metabolism; D011993:Recombinant Fusion Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000276:immunology* / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011993:Recombinant Fusion Proteins; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2