Ectopic Germinal Centers Are Rare in Sjogren's Syndrome Salivary Glands and Do Not Exclude Autoreactive B Cells

• Published in: The Journal of immunology (1950) 2009-03, Vol.182 (6), p.3540-3547
• Main Authors: Le Pottier, Laetitia, Devauchelle, Valerie, Fautrel, Alain, Daridon, Capucine, Saraux, Alain, Youinou, Pierre, Pers, Jacques-Olivier
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Autoantibodies - biosynthesis; Autoantibodies - metabolism; B-Lymphocyte Subsets - immunology; B-Lymphocyte Subsets - metabolism; B-Lymphocyte Subsets - pathology; Child; Child, Preschool; Cytidine Deaminase - biosynthesis; Cytidine Deaminase - genetics; Female; Germinal Center - immunology; Germinal Center - metabolism; Germinal Center - pathology; Humans; Immunology; Immunophenotyping; Life Sciences; Middle Aged; Palatine Tonsil - cytology; Palatine Tonsil - immunology; Palatine Tonsil - metabolism; Salivary Glands - immunology; Salivary Glands - metabolism; Salivary Glands - pathology; Sjogren's Syndrome - immunology; Sjogren's Syndrome - metabolism; Sjogren's Syndrome - pathology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.0803588

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.