title: TLR9 responses of B cells are repressed by intravenous immunoglobulin through the recruitment of phosphatase.
abstract: One way for intravenous Ig (IVIg) to affect responses of the B cells might be to operate through their TLR7 and TLR9. We confirm the ability of TLR agonists to induce CD25 expression in B cells. For this to occur, sialylated Fc-gamma of IgG included in the IVIg preparation are required. As a result, IVIg suppresses TLR-induced production of the proinflammatory IL-6, but not that of the anti-inflammatory IL-10. That is, IVIg mimics the effects of the MyD88 inhibitor. Finally, as we previously showed that IVIg induces CD22 to recruit the inhibitory SHP-1, we established that this enzyme was also involved in IVIg-induced inhibition of TLR9 signaling. This is the first report to demonstrate such a mechanism underlying the negative impact of IVIg on B lymphocytes.
authors.affiliation: Université Européenne de Bretagne, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Séité
authors.forename: Thomas
authors.initials: T
authors.lastname: Guerrier
authors.forename: Divi
authors.initials: D
authors.lastname: Cornec
authors.forename: Christophe
authors.initials: C
authors.lastname: Jamin
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.forename: Sophie
authors.initials: S
authors.lastname: Hillion
mesh_terms: D000595:Amino Acid Sequence; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000276:immunology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051918:Sialic Acid Binding Ig-like Lectin 2 / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*; D051199:Toll-Like Receptor 7 / Q000819:agonists / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000819:agonists / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C497867:CD22 protein, human; C508017:IL2RA protein, human; D016756:Immunoglobulins, Intravenous; D053645:Interleukin-2 Receptor alpha Subunit; D015850:Interleukin-6; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D009838:Oligodeoxyribonucleotides; D051918:Sialic Acid Binding Ig-like Lectin 2; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D016753:Interleukin-10; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6