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  • Review Article
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B cells in the pathogenesis of primary Sjögren syndrome

Nature Reviews Rheumatology volume 14, pages 133–145 (2018)Cite this article

Subjects

Key Points

  • Genetic risk factors associated with primary Sjögren syndrome (pSS) can promote B cell activation, as can epigenetic changes, which can sometimes affect the same disease-associated genes.

  • BAFF (also known as TNF ligand superfamily member 13B) is central to the crosstalk between early activation of the innate immune system and the stimulation of autoreactive B cells.

  • CD27+ memory B cells, marginal zone B cells, plasmablasts and plasma cells are the key subsets of B cells involved in the pathogenesis of pSS.

  • Target organs (salivary and lachrymal glands) are involved in B cell activation, notably via the formation of germinal centre-like structures within the epithelium and plasma cell niches.

  • Continuous stimulation of autoreactive B cells by immune complexes is the first step towards lymphomagenesis associated with pSS.

  • Continuously activated autoreactive B cells need to be tightly controlled by genetic factors and by the tissue microenvironment as subtle defects in these controls might promote clonal escape and lymphomagenesis.

Abstract

Primary Sjögren syndrome (pSS) is a prototypical autoimmune disease. The involvement of B cells in the pathogenesis of pSS has long been suspected on the basis of clinical observations that include the presence of serum autoantibodies, hypergammaglobulinaemia, increased levels of free light chains and increased risk of B cell lymphoma. Moreover, the composition of the B cell subset is altered in pSS. In this Review, we discuss the mechanisms that support the increased activation of B cells in pSS, including genetic and epigenetic factors and environmental triggers that promote B cell activation via the innate immune system. B cell activating factor (BAFF, also known as TNF ligand superfamily member 13B) is at the crossroads of this process. An important role also exists for the target tissue (exocrine glands, namely the salivary and lachrymal glands), which promotes local B cell activation. This continuous stimulation of B cells is the main driver of lymphomatous escape. Identification of the multiple steps that support B cell activation has led to the development of promising targeted therapies that will hopefully lead to the development of an efficient therapeutic strategy for pSS.

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Figure 1: B cell activation in salivary glands.
Figure 2: The pathophysiology of primary Sjögren syndrome-associated lymphoma.

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Acknowledgements

The work of the authors was supported financially by the Fondation Pour La Recherche Médicale DEQ20150934719: Sjögren's Syndrome and Autoimmunity-Associated Lymphomas (SAIL).

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  1. Department of Rheumatology, Université Paris-Sud, INSERM U1184: Centre for Immunology of Viral Infections and Autoimmune Diseases, Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpitaux Universitaires Paris-Sud Bicêtre, Le Kremlin-Bicêtre, France

    Gaëtane Nocturne & Xavier Mariette

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  1. Gaëtane Nocturne
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All authors researched the data for the article, provided substantial contributions to discussions of its content, wrote the article and reviewed and/or edited the manuscript before submission.

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Correspondence to Xavier Mariette.

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Nocturne, G., Mariette, X. B cells in the pathogenesis of primary Sjögren syndrome. Nat Rev Rheumatol 14, 133–145 (2018). https://doi.org/10.1038/nrrheum.2018.1

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