B cells in the pathogenesis of primary Sjögren syndrome

Nat Rev Rheumatol. 2018 Mar;14(3):133-145. doi: 10.1038/nrrheum.2018.1. Epub 2018 Feb 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • B-Cell Activating Factor / genetics*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / pathology
  • Epigenesis, Genetic
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Lymphocyte Activation
  • Sjogren's Syndrome / genetics*
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology


  • B-Cell Activating Factor
  • TNFSF13B protein, human