Role of Toll-like receptors in primary Sjögren's syndrome with a special emphasis on B-cell maturation within exocrine tissues

Journal of Autoimmunity
Thomas GuerrierPierre Youinou

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.

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Citations

Sep 10, 2013·Journal of Autoimmunity·Pietro Invernizzi
Jun 4, 2013·Immunotherapy·Divi CornecJacques-Olivier Pers
Mar 28, 2013·Pharmacology & Therapeutics·Jing LiHang Yin
Mar 12, 2015·Frontiers in Oncology·Christina Arieta Kuksin, Lisa M Minter
Apr 10, 2017·Journal of Autoimmunity·Erlin A HaackeFrans G M Kroese
Mar 8, 2014·Journal of Autoimmunity·Ayan LahiriJacques-Olivier Pers
May 22, 2016·International Journal of Immunopathology and Pharmacology·Sarah BenchabaneChafia Touil-Boukoffa
May 23, 2014·Immunologic Research·Claire M Buchta, Gail A Bishop
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Jan 11, 2019·International Journal of Molecular Sciences·Austin K MircheffChuanqing Ding
Mar 1, 2021·Journal of Autoimmunity·Anna-Karin E Palm, Sandra Kleinau

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