title: Importance of Toll-like receptors for B lymphocyte survival in primary Sjögren's syndrome.
abstract: The Sjögren's syndrome is a systemic autoimmune disease characterized by lymphocytic infiltration of the glands responsible for mouth and eyes dryness. A minority of infiltrating B cells is organized as germinal centers while the majority is aggregated into clusters of transitional and marginal zone B cells. The Toll-like receptor 9 (TLR9) recognizes microbial DNA but also, sometimes, the self DNA. It appears to be a key determinant of the survival and differentiation of B lymphocytes. After laser micro-dissection of B cells from salivary glands, analyses by quantitative RT-PCR showed that transitional B cells express high level of TLR9 mRNA unlike B cells from germinal centers. B lymphocytes from healthy donors were sorted by flow cytometry and stimulated in vitro with their TLR9. It induces survival, activation and proliferation associated with phenotypic changes. Transitional B cells exhibited characteristics of the marginal zone, whereas mature B cells expressed follicular germinal center specificities. Finally, IgM and IgG were secreted by both population, but with elevated production of autoantibodies by the transitional B cells. Increased expression of TLR9 by transitional B cells suggests that they may be highly sensitive to differentiate into autoantibody secreting cells through maturation into the marginal zone into the salivary glands. TLR9 might be a target for forthcoming biotherapies.
authors.affiliation: EA2216 "Immunology & Pathology" and IFR 148 ScinBioS, Université Européenne de Bretagne, Brest, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guerrier
authors.affiliation: EA2216 "Immunology & Pathology" and IFR 148 ScinBioS, Université Européenne de Bretagne, Brest, France.
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Le Pottier
authors.affiliation: EA2216 "Immunology & Pathology" and IFR 148 ScinBioS, Université Européenne de Bretagne, Brest, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.affiliation: EA2216 "Immunology & Pathology" and IFR 148 ScinBioS, Université Européenne de Bretagne, Brest, France.
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
authors.affiliation: EA2216 "Immunology & Pathology" and IFR 148 ScinBioS, Université Européenne de Bretagne, Brest, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Jamin
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000032:analysis; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002449:Cell Aggregation / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018899:CpG Islands / Q000276:immunology; D005260:Female; D005312:Fetal Blood; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D007075:Immunoglobulin M / Q000032:analysis; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology; D054448:Precursor Cells, B-Lymphoid / Q000187:drug effects / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D012469:Salivary Glands / Q000166:cytology / Q000276:immunology; D012859:Sjogren's Syndrome / Q000276:immunology*; D051217:Toll-Like Receptor 9 / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001323:Autoantibodies; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9