title: Role of Toll-like receptors in primary Sjögren's syndrome with a special emphasis on B-cell maturation within exocrine tissues.
abstract: Be they follicular cells within the germinal centers (GCs) or marginal zone (MZ), all naïve mature B lymphocytes need tonic signaling to stay alive. We reasoned that the same holds true for those B lymphocytes that proliferate in the salivary glands (SGs) of patients with primary Sjögren's syndrome. Based on B cell infiltration, 11 SGs and three tonsil samples were selected for further examination. Tissue sections were stained using CD20 combined with CD10, CD21, CD27, CD38 or IgD. They were also laser-microdissected for quantitative RT-PCR of transcription factors, GC-specific activation-induced cytidine deaminase (AID) and TLR9. Some B cell aggregates proved to be real GCs according to their membrane markers, whereas others were clusters of transitional type II B cells. These contained mRNAs for Notch-2 and Blimp-1, but not for Pax-5, Bcl-6 and AID. Unanticipated was the finding of mRNAs for TLR9 in these clusters of MZ B-cells, but not in the real GCs. Not only do TLR9 deliver sufficiency of tonic signaling to keep B cells alive, but they also confer autoreactive B cells with an MZ-like phenotype. Thus, TLRs might be targets for forthcoming biotherapies.
authors.affiliation: EA2216 Immunology & Pathology and IFR 148 ScinBioS, Université Européenne de Bretagne, Université de Brest, Brest, France.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guerrier
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Le Pottier
authors.forename: Valérie
authors.initials: V
authors.lastname: Devauchelle
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
authors.forename: Christophe
authors.initials: C
authors.lastname: Jamin
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000032:analysis; D000293:Adolescent; D000328:Adult; D000368:Aged; D018951:Antigens, CD20 / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000096:biosynthesis; D005260:Female; D018858:Germinal Center / Q000378:metabolism; D006801:Humans; D007072:Immunoglobulin D / Q000032:analysis; D008875:Middle Aged; D014066:Palatine Tonsil; D000074462:Positive Regulatory Domain I-Binding Factor 1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000032:analysis; D017452:Receptors, IgG / Q000032:analysis; D012097:Repressor Proteins / Q000096:biosynthesis; D012470:Salivary Glands, Minor / Q000276:immunology* / Q000378:metabolism; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis
chemical_list: D018951:Antigens, CD20; D007072:Immunoglobulin D; D012333:RNA, Messenger; D017464:Receptors, Complement 3d; D017452:Receptors, IgG; D012097:Repressor Proteins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C087042:PRDM1 protein, human; D000074462:Positive Regulatory Domain I-Binding Factor 1; D051997:ADP-ribosyl Cyclase 1; D003564:Cytidine Deaminase