title: Ectopic germinal centers are rare in Sjogren's syndrome salivary glands and do not exclude autoreactive B cells.
abstract: This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren's syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren's syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20(+)IgD(-)CD38(+)CD21(+)CD24(-) B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed "real GCs". CD20(+)IgD(+)CD38(-)CD21(+)CD24(+) B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed "aggregates". Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.
authors.affiliation: Equipe d'Accueil 2216 and Institut Fédératif de Recherche 418, Science et Ingénierie en Biologie-Santé, Université de Brest, Brest, and Université Européenne de Bretagne, Brest, France.
authors.forename: Laëtitia
authors.initials: L
authors.lastname: Le Pottier
authors.forename: Valérie
authors.initials: V
authors.lastname: Devauchelle
authors.forename: Alain
authors.initials: A
authors.lastname: Fautrel
authors.forename: Capucine
authors.initials: C
authors.lastname: Daridon
authors.forename: Alain
authors.initials: A
authors.lastname: Saraux
authors.forename: Pierre
authors.initials: P
authors.lastname: Youinou
authors.forename: Jacques-Olivier
authors.initials: JO
authors.lastname: Pers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D003564:Cytidine Deaminase / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D018858:Germinal Center / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D016130:Immunophenotyping; D008875:Middle Aged; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D001323:Autoantibodies; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase