B cells in Sjögren's syndrome: from pathophysiology to diagnosis and treatment

J Autoimmun. 2012 Sep;39(3):161-7. doi: 10.1016/j.jaut.2012.05.014. Epub 2012 Jun 30.


Primary Sjögren's syndrome (pSS) is a chronic autoimmune systemic disease, characterized by a lymphoplasmocytic infiltration and a progressive destruction of salivary and lachrymal glands, leading to ocular and mouth dryness. T cells were originally considered to play the initiating role in the autoimmune process, while B cells were restricted to autoantibody production. However, recent years have seen growing evidence that the roles of B cells in pSS pathophysiology are multiple, and that these cells may actually play a central role in the development of the disease. B cells are over-stimulated and produce excessive amounts of immunoglobulins and various autoantibodies. Peripheral blood and salivary-gland B-cell subset distribution is altered, leading to the constitution of ectopic germinal centers where auto-reactive clones may escape tolerance checkpoints. B cells control T-cell activation by different means: B effector cells guide Th1 or Th2 differentiation, whereas regulatory B cells inhibit T-cell proliferation. Several B-cell specific cytokines, such as BAFF or Flt-3L, are instrumental in the occurrence of B-cell dysfunction. Chronic and excessive stimulation of B cells may lead to the development of lymphoma in pSS patients. Autoantibodies and blood B-cell subset analysis are major contributors of a clinical diagnosis of pSS. These considerations led to the development of B-cell depletion therapies for the management of pSS. Rituximab, a monoclonal antibody to CD20, is the best studied biologics in pSS, but other treatments hold promise, targeting for example CD22 or BAFF. Thus, during the last 20 years, the understanding of the multifaceted roles of B cells in pSS has revolutionized the management of this complex disease.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Autoantibodies / biosynthesis*
  • Autoantibodies / immunology
  • B-Cell Activating Factor / antagonists & inhibitors
  • B-Cell Activating Factor / immunology
  • B-Lymphocyte Subsets / drug effects*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / pathology
  • Cell Proliferation
  • Humans
  • Lacrimal Apparatus / drug effects
  • Lacrimal Apparatus / immunology
  • Lacrimal Apparatus / pathology
  • Lymphocyte Activation
  • Lymphocyte Depletion
  • Salivary Glands / drug effects
  • Salivary Glands / immunology
  • Salivary Glands / pathology
  • Sialic Acid Binding Ig-like Lectin 2 / antagonists & inhibitors
  • Sialic Acid Binding Ig-like Lectin 2 / immunology
  • Sjogren's Syndrome / diagnosis
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / physiopathology
  • Sjogren's Syndrome / therapy*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / pathology
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / immunology


  • Antibodies, Monoclonal
  • Autoantibodies
  • B-Cell Activating Factor
  • Sialic Acid Binding Ig-like Lectin 2
  • TNFSF13B protein, human
  • FLT3 protein, human
  • fms-Like Tyrosine Kinase 3