title: TLR9 expressed on plasma membrane acts as a negative regulator of human B cell response.
abstract: Toll-like receptors (TLRs) are positioned at the interface between innate and adaptive immunity. Unlike others, those such as TLR9, that recognize nucleic acids, are confined to the endosomal compartment and are scarce on the cell surface. Here, we present evidence for TLR9 expression on the plasma membrane of B cells. In contrast to endosomal TLR9, cell surface TLR9 does not bind CpG-B oligodeoxynucleotides. After B cell-receptor (BCR) stimulation, TLR9 was translocated into lipid rafts with the BCR, suggesting that it could serve as a co-receptor for BCR. Nevertheless, stimulation of B cells with anti-TLR9 antibodies did not modify the BCR-induced responses despite up-regulation of tyrosine phosphorylation of proteins. However, CpG-B activation of B cells, acting synergistically with BCR signals, was inhibited by anti-TLR9 stimulation. Induction of CD25 expression and proliferation of B cells were thus down-regulated by the engagement of cell surface TLR9. Overall, our results indicate that TLR9 expressed on the plasma membrane of B cells might be a negative regulator of endosomal TLR9, and could provide a novel control by which activation of autoreactive B cells is restrained.
authors.affiliation: EA2216 Immunologie et Pathologie, LabEx IGO, SFR ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guerrier
authors.affiliation: EA2216 Immunologie et Pathologie, LabEx IGO, SFR ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Pochard
authors.affiliation: EA2216 Immunologie et Pathologie, LabEx IGO, SFR ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France.
authors.forename: Ayan
authors.initials: A
authors.lastname: Lahiri
authors.affiliation: EA2216 Immunologie et Pathologie, LabEx IGO, SFR ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France; Laboratory of Immunology and Immunotherapy, CHRU Brest, Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.affiliation: EA2216 Immunologie et Pathologie, LabEx IGO, SFR ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France; Laboratory of Immunology and Immunotherapy, CHRU Brest, Brest, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
authors.affiliation: EA2216 Immunologie et Pathologie, LabEx IGO, SFR ScInBioS, Université de Brest et Université Européenne de Bretagne, Brest, France; Laboratory of Immunology and Immunotherapy, CHRU Brest, Brest, France. Electronic address: christophe.jamin@univ-brest.fr.
authors.forename: Christophe
authors.initials: C
authors.lastname: Jamin
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D056747:Immunomodulation; D016130:Immunophenotyping; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D011485:Protein Binding; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: C408982:CPG-oligonucleotide; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9
keywords: B lymphocytes; Cell surface; CpG-B; Negative regulator; Stimulation; TLR9